Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months

Abstract

Importance: Emotion regulation is critically disrupted in depression, and the use of paradigms that tap into these processes may uncover essential changes in neurobiology during treatment. In addition, because neuroimaging outcome studies of depression commonly use only baseline and end-point data-which are more prone to week-to-week noise in symptomatology-we sought to use all data points over the course of a 6-month trial.

Objective: To examine changes in neurobiology resulting from successful treatment.

Design, setting, and participants: Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from 1 of 2 antidepressant treatments during a 6-month trial. Twenty-one patients with major depressive disorder and without other Axis I or Axis II diagnoses were scanned before treatment and 2 and 6 months into treatment at the university's functional magnetic resonance imaging facility.

Interventions: Venlafaxine hydrochloride extended release (with doses of up to 300 mg) or fluoxetine hydrochloride (with doses of up to 80 mg).

Main outcomes and measures: Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm, as well as regular assessments of symptom severity using the Hamilton Depression Rating Scale. For use of all data points, slope trajectories were calculated for rate of change in depression severity and for rate of change in neural engagement.

Results: The depressed individuals who showed the steepest decrease in depression severity over the 6-month period were the same individuals who showed the most rapid increases in activity in Brodmann area 10 and the right dorsolateral prefrontal cortex activity when regulating negative affect over the same time frame. This relationship was more robust when using only the baseline and end-point data.

Conclusions and relevance: Changes in prefrontal cortex engagement when regulating negative affect correlate with changes in depression severity over 6 months. These results are buttressed by calculating these statistics, which are more reliable and robust to week-to-week variation than are difference scores.

Figures

Figure 1

Schematic of the emotion regulation paradigm. This is an example trial in which a positive image was presented. Four seconds into image presentation, participants received an auditory prompt instructing them to “enhance”, “suppress”, or “attend” to their affect.

Figure 2

Time course of HAMD scores over time for MDD patients completing the six month trial.

Figure 3

When regulating negative affect, BA10 and RDLPFC trajectory over six months demonstrate significant associations with HAMD trajectory over the same time. Dark blue points are depression “remitters” (HAMD score ≤ 7), pink dots are “non remitters”.