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

Soonjo Hwang,Ellen Leibenluft,James Blair,Yongmin Chang,Christopher Kratochvil,Ji-Woo Suk,Harma Meffert,Unsun Chung,Eunji Kim

doi:10.1089/cap.2020.0174

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).

Highlights

Childhood trauma and maltreatment are the most common forms of early life stress (ELS) and are associated with significant mental health risks (Agorastos et al 2019)
Youths with disruptive behavior disorders (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 and emotional regulation; and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas and an emotion regulation area
This study provides preliminary evidence that a serotonergic agent can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of topdown attention control and emotion regulation areas

Summary

Introduction

Childhood trauma and maltreatment are the most common forms of early life stress (ELS) and are associated with significant mental health risks (Agorastos et al 2019). Large epidemiological studies report that more than one in four children experience a significant traumatic event such as child abuse, domestic/community/ school violence, vehicular accident, or other shocking/terrifying experiences (Costello et al 2002; Cohen et al 2010). These children are at increased risk for the development of significant and potentially long-lasting mental health problems (Cohen et al 2010), including internalizing (anxiety, depression) and, of particular interest here, externalizing (aggression) behavior (Thornberry et al 2001; Lansford et al 2002).

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