Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study

Abstract

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC).

Keywords: disruptive behavior disorder; fluoxetine; insula; trauma; ventromedial prefrontal cortex.

FIG. 1.

Facial expression task. In this task, all the participants were asked to determine the gender of the faces. Faces are presented with parametrically modulated intensity [25% (A), neutral (B), 150% (C), and 100% (D)] of fearful expressions.

FIG. 2.

(1) Region of interest ventromedial prefrontal cortex (coordinates: −4, 40, −3); (2) ROI amygdala (coordinates: −25, −1, −21); (3) insula cortex (coordinates: −34, 2, −10); (4) postcentral gyrus (coordinates: −37, −25, 47); and (5) inferior parietal lobule (coordinates: −61, −34, 32) showing a significant group by time interaction; (6–10) In all those areas except amygdala, weighted BOLD responses to fearful expression were significantly increased in youths with DBDs who received fluoxetine after the treatment, compared to youths with DBDs and without fluoxetine treatment, as well as healthy youths. In amygdala, weighted BOLD responses to fearful expression were significantly decreased in youths with DBDs who received fluoxetine after the treatment, compared to youths with DBDs and without fluoxetine treatment [BOLD responses: (6) ventromedial prefrontal cortex, (7) amygdala, (8) insula cortex, (9) postcentral gyrus, and (10) inferior parietal lobule]. BOLD, blood oxygen level dependent; DBD, disruptive behavior disorder. Color images are available online.