Neural Dysregulation in Posttraumatic Stress Disorder

Sripada, Rebecca K.; King, Anthony P.; Welsh, Robert C.; Garfinkel, Sarah N.; Wang, Xin; Sripada, Chandra; Liberzon, Israel

doi:10.1097/psy.0b013e318273bf33

Cited by 351 publications

(245 citation statements)

References 67 publications

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“…We support and extend these findings by showing that this hyperactivation is particularly important for persistence of PTSD. Furthermore, structural (Long et al, 2013) and functional resting state connectivity studies (Sripada et al, 2012) have revealed increased connectivity within the salience network in PTSD patients. A recent graph analysis study showed a relationship between insula decoupling and reexperiencing symptoms in PTSD patients, indicating disrupted salience determination (Spielberg et al, 2015).…”

Section: Discussionmentioning

confidence: 98%

Predicting Treatment Outcome in PTSD: A Longitudinal Functional MRI Study on Trauma-Unrelated Emotional Processing

Rooij

Kennis

Vink

et al. 2015

Neuropsychopharmacol

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In about 30-50% of patients with posttraumatic stress disorder (PTSD), symptoms persist after treatment. Although neurobiological research has advanced our understanding of PTSD, little is known about the neurobiology underlying persistence of PTSD. Two functional MRI scans were collected from 72 war veterans with and without PTSD over a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. All participants performed a trauma-unrelated emotional processing task in the scanner. Based on post-treatment symptom severity, a distinction was made between remitted and persistent patients. Behavioral and imaging measures of trauma-unrelated emotional processing were compared between the three groups (remitted patients, N=21; persistent patients, N=22; and combat controls, N=25) with repeated-measures (pre- and post-treatment) analyses. Second, logistic regression was used to predict treatment outcome. Before and after treatment, persistent patients showed a higher dorsal anterior cingulate cortex (dACC) and insula response to negative pictures compared with remitted patients and combat controls. Before treatment, persistent patients showed increased amygdala activation in response to negative pictures compared with remitted patients. The remitted patients and combat controls did not differ on the behavioral or imaging measures. Finally, higher dACC, insula, and amygdala activation before treatment were significant predictors of symptom persistence. Our results highlight a pattern of brain activation that may predict poor response to PTSD treatment. These findings can contribute to the development of alternative or additional therapies. Further research is needed to elucidate the heterogeneity within PTSD and describe how differences in neural function are related to treatment outcome. Such approaches are critical for defining parameters to customize PTSD treatment and improve treatment response rates.

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Section: Discussionmentioning

confidence: 98%

Predicting Treatment Outcome in PTSD: A Longitudinal Functional MRI Study on Trauma-Unrelated Emotional Processing

Rooij

Kennis

Vink

et al. 2015

Neuropsychopharmacol

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“…(2012), for conflicting findings). Among patients with PTSD, however, it is more common to observe disruptions in DMN integration (Bluhm et al., 2009; Rabellino et al., 2015; Sripada et al., 2012) where it has been proposed that early‐life trauma disrupts the integration of the DMN (Daniels et al., 2010). Despite having a history of trauma exposure, the primary diagnosis among our patient sample was MDD, and the timing, type, and frequency of trauma were heterogenous among participants.…”

Section: Discussionmentioning

confidence: 99%

Relation between patterns of intrinsic network connectivity, cognitive functioning, and symptom presentation in trauma‐exposed patients with major depressive disorder

et al. 2017

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ObjectiveThe present study investigated resting fMRI connectivity within the default mode (DMN), salience (SN), and central executive (CEN) networks in relation to neurocognitive performance and symptom severity in trauma‐exposed patients with major depressive disorder (MDD).MethodGroup independent component analysis was conducted among patients with MDD (n = 21), examining DMN, SN, and CEN connectivity in relation to neurocognitive performance and symptom severity. Activation in these networks was also compared between the patient group and healthy controls (n = 20).ResultsAmong the patient group, higher levels of performance on measures of verbal memory and executive functioning were related to increased connectivity within the DMN (i.e., inferior parietal lobe; precuneus). Greater depression severity was related to reduced connectivity between the SN and a node of the DMN (i.e., posterior cingulate cortex) and higher depersonalization symptoms were related to enhanced connectivity between the SN and a node of the DMN (i.e., middle temporal gyrus). Higher symptoms of depersonalization were also associated with reduced integration of the DMN with the medial frontal gyrus. Relative to controls, patients with MDD showed greater connectivity of the ventromedial prefrontal cortex within the DMN.ConclusionIntrinsic connectivity network patterns are related to cognitive performance and symptom presentation among trauma‐exposed patients with MDD.

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“…Putative neural mechanisms underlying their pathogenic effect may involve a combination of a hyperactive emotional reactivity system coupled with dysfunctional regulatory circuitry in the frontal lobes (Etkin & Wager, 2007; Hayes, Hayes, & Mikedis, 2012; Pitman et al, 2012). Beyond the fronto-limbic circuitry, aberrations between and within (Sripada et al, 2012) the default mode network (DMN), salience network (SN), and the central executive network (CEN) were demonstrated in PTSD. The DMN and CEN were found to be weakly interconnected and hypoactive, hypothetically destabilized by an overactive and hyper-connected SN and a low saliency perception threshold, along with inefficient DMN-CEN modulation (Akiki, Averill, & Abdallah, 2017).…”

Section: Introductionmentioning

confidence: 99%

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol

Fine

Achituv

Etkin

et al. 2018

European Journal of Psychotraumatology

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Background: The immediate aftermath of traumatic events is a period of enhanced neural plasticity, following which some survivors remain with post-traumatic stress disorder (PTSD) whereas others recover. Evidence points to impairments in emotional reactivity, emotion regulation, and broader executive functions as critically contributing to PTSD. Emerging evidence further suggests that the neural mechanisms underlying these functions remain plastic in adulthood and that targeted retraining of these systems may enhance their efficiency and could reduce the likelihood of developing PTSD. Administering targeted neurocognitive training shortly after trauma exposure is a daunting challenge. This work describes a study design addressing that challenge. The study evaluated the direct effects of cognitive remediation training on neurocognitive mechanisms that hypothetically underlay PTSD, and the indirect effect of this intervention on emerging PTSD symptoms. Method: We describe a study rationale, design, and methodological choices involving: (a) participants’ enrolment; (b) implementation and management of a daily self-administered, web-based intervention; (c) reliable, timely screening and assessment of treatment of eligible survivors; and (d) defining control conditions and outcome measures. We outline the rationale of choices made regarding study sample, timing of intervention, measurements, monitoring participants’ adherence, and ways to harmonize and retain interviewers’ fidelity and mitigate eventual burnout by repeated contacts with recently traumatized survivors. Conclusion: Early web-based interventions targeting causative mechanisms of PTSD can be informed by the model presented in this paper.

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Neural Dysregulation in Posttraumatic Stress Disorder

Cited by 351 publications

References 67 publications

Predicting Treatment Outcome in PTSD: A Longitudinal Functional MRI Study on Trauma-Unrelated Emotional Processing

Predicting Treatment Outcome in PTSD: A Longitudinal Functional MRI Study on Trauma-Unrelated Emotional Processing

Relation between patterns of intrinsic network connectivity, cognitive functioning, and symptom presentation in trauma‐exposed patients with major depressive disorder

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol

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