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Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma.

ABSTRACT: Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for posttraumatic stress disorder (PTSD); however, our understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospective study of PTSD.Participants were recruited from the emergency department of a large level I trauma center within 24 hours of trauma. PTSD symptoms were assessed at baseline and approximately 1, 3, 6, and 12 months after trauma. Growth curve modeling was used to estimate symptom recovery trajectories. Thirty-one individuals participated in functional magnetic resonance imaging around the 1-month assessment, passively viewing fearful and neutral face stimuli. Reactivity (fearful > neutral) and habituation to fearful faces was examined.Amygdala reactivity, but not habituation, 5 to 12 weeks after trauma was positively associated with the PTSD symptom intercept and predicted symptoms at 12 months after trauma. Habituation in the ventral anterior cingulate cortex was positively associated with the slope of PTSD symptoms, such that decreases in ventral anterior cingulate cortex activation over repeated presentations of fearful stimuli predicted increasing symptoms.Findings point to neural signatures of risk for maintaining PTSD symptoms after trauma exposure. Specifically, chronic symptoms were predicted by amygdala hyperreactivity, and poor recovery was predicted by a failure to maintain ventral anterior cingulate cortex activation in response to fearful stimuli. The importance of identifying patients at risk after trauma exposure is discussed.

SUBMITTER: Stevens JS

PROVIDER: S-EPMC5449257 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma.

Stevens Jennifer S JS Kim Ye Ji YJ Galatzer-Levy Isaac R IR Reddy Renuka R Ely Timothy D TD Nemeroff Charles B CB Hudak Lauren A LA Jovanovic Tanja T Rothbaum Barbara O BO Ressler Kerry J KJ

Biological psychiatry 20161223 12

<h4>Background</h4>Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for posttraumatic stress disorder (PTSD); however, our understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospecti ...[more]

PMID: 28117048

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Project description:Working memory is critically involved in ignoring emotional distraction while maintaining goal-directed behavior. Antagonistic interactions between brain regions implicated in emotion processing, e.g., amygdala, and brain regions involved in cognitive control, e.g., dorsolateral and dorsomedial prefrontal cortex (dlPFC, dmPFC), may play an important role in coping with emotional distraction. We previously reported prolonged reaction times associated with amygdala hyperreactivity during emotional distraction in interpersonally traumatized borderline personality disorder (BPD) patients compared to healthy controls (HC): Participants performed a working memory task, while neutral versus negative distractors (interpersonal scenes from the International Affective Picture System) were presented. Here, we re-analyzed data from this study using psychophysiological interaction analysis. The bilateral amygdala and bilateral dorsal anterior cingulate cortex (dACC) were defined as seed regions of interest. Whole-brain regression analyses with reaction times and self-reported increase of dissociation were performed. During emotional distraction, reduced amygdala connectivity with clusters in the left dorsolateral and ventrolateral PFC was observed in the whole group. Compared to HC, BPD patients showed a stronger coupling of both seeds with a cluster in the right dmPFC and stronger positive amygdala connectivity with bilateral (para)hippocampus. Patients further demonstrated stronger positive dACC connectivity with left posterior cingulate, insula, and frontoparietal regions during emotional distraction. Reaction times positively predicted amygdala connectivity with right dmPFC and (para)hippocampus, while dissociation positively predicted amygdala connectivity with right ACC during emotional distraction in patients. Our findings suggest increased attention to task-irrelevant (emotional) social information during a working memory task in interpersonally traumatized patients with BPD.

Project description:OBJECTIVE:The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence. METHOD:Sixty-four adolescents were stratified into higher- or lower-childhood-trauma groups. Inhibitory control was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging assessed neural correlates of stress in adolescents. RESULTS:Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, associated with Stroop Color-Word task performance in prior meta-analyses, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r?=?-.23, p?=?.04). Childhood trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction?=?-1.26, p?=?.02, 95%CI?=?-2.33,-0.20), where Stroop errors were inversely associated with brain activation among those with higher childhood trauma (simple slopes?=?-.83, p?=?.007, 95%CI?=?-1.40,-0.25). Low stress-related rCZa activation inversely (R2?=?0.19, b?=?-0.43, p?=?.001, 95%CI?=?-4.11,-1.06) and Stroop errors directly (R2?=?0.09, b?=?0.27, p?=?.048, 95%CI?=?0.02, 5.8) associated with baseline subjective anxiety while controlling for childhood trauma. CONCLUSIONS:This is the first study to demonstrate a moderating role of childhood trauma on the relationship between inhibitory control and stress-related ACC activation. Childhood trauma may portend neurodevelopmental changes that impede recruitment of control-associated ACC-functioning during distress, which may relate to dysregulation of stress-induced affective responses. Further work is needed to elucidate relationships between childhood trauma and addictive behaviors precipitated by stress.

Project description:BackgroundPosttraumatic stress disorder (PTSD) is characterized as a disorder of exaggerated defensive physiological arousal. The novel aim of the present research was to investigate within PTSD a potential dose-response relationship between past trauma recurrence and current comorbidity and intensity of physiological reactions to imagery of trauma and other aversive scenarios.MethodsA community sample of principal PTSD (n = 49; 22 single-trauma exposed, 27 multiple-trauma exposed) and control (n = 76; 46 never-trauma exposed, 30 trauma exposed) participants imagined threatening and neutral events while acoustic startle probes were presented and the eye-blink response (orbicularis occuli) was recorded. Changes in heart rate, skin conductance level, and facial expressivity were also indexed.ResultsOverall, PTSD patients exceeded control participants in startle reflex, autonomic responding, and facial expressivity during idiographic trauma imagery and, though less pronounced, showed heightened reactivity to standard anger, panic, and physical danger imagery. Concerning subgroups, control participants with and without trauma exposure showed isomorphic patterns. Within PTSD, only the single-trauma patients evinced robust startle and autonomic responses, exceeding both control participants and multiple-trauma PTSD. Despite greater reported arousal, the multiple-trauma relative to single-trauma PTSD group showed blunted defensive reactivity associated with more chronic and severe PTSD, greater mood and anxiety disorder comorbidity, and more pervasive dimensional dysphoria (e.g., depression, trait anxiety).ConclusionsWhereas PTSD patients generally show marked physiological arousal during aversive imagery, concordant with self-reported distress, the most symptomatic patients with histories of severe, cumulative traumatization show discordant physiological hyporeactivity, perhaps attributable to sustained high stress and an egregious, persistent negative affectivity that ultimately compromises defensive responding.

Dataset Information

Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma.

Publications

Amygdala Reactivity and Anterior Cingulate Habituation Predict Posttraumatic Stress Disorder Symptom Maintenance After Acute Civilian Trauma.

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