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Book ; Thesis: Neurobiological underpinnings of trauma-related psychopathology

Sierk, Anika

2018

Abstract: The understanding and treatment of trauma-related psychopathology is a crucial challenge in the field of global mental health today. The etiology and mechanisms of two common traumarelated symptoms - intrusive re-experiencing and dissociative ... ...

Title translation	Neurobiologische Untermauerung der traumabezogenen Psychopathologie
Abstract	The understanding and treatment of trauma-related psychopathology is a crucial challenge in the field of global mental health today. The etiology and mechanisms of two common traumarelated symptoms - intrusive re-experiencing and dissociative symptomatology - are still not well understood. The present work aims to advance the understanding of these phenomena by investigating their neurobiological underpinnings in two disorders: depersonalization/derealization disorder (DPD), in which dissociation depicts the core feature, and the dissociative subtype of posttraumatic stress disorder (PTSD-D), in which dissociative symptomatology and intrusive re-experiencing co-occur and correlate in regard to their severity. Alterations in fiber tract networks in white matter, which are crucial for communicating between brain regions, have not yet been investigated in DPD or PTSD-D. In Study I, white matter network alterations were explored in 23 patients with DPD compared to 23 matched healthy controls. Results yielded relatively lower structural connectivity in left and right temporal regions in DPD, which have previously been associated with dissociative symptomatology in DPD and in other disorders. Furthermore, a trend indicated alterations in a fronto-limbic circuit, which a neurobiological model proposes underlies dissociation in DPD as well as PTSD-D. In Study II, we tested whether fronto-limbic circuits are also altered in PTSD-D (n=23) compared to 'classic' PTSD patients (n=19) using the same analysis pipeline as in Study I. No respective white matter changes were detected on a network level in PTSD-D. However, subsequent exploratory analyses revealed alterations in two subcortical networks comprising a limbic-thalamic circuit and low-level motor regions, respectively. The limbicthalamic network is crucial for declarative and spatial mnemonic processes, which according to dual memory models play a crucial role for the development of intrusive memories. We tested the respective memory model in Study III and confirmed for the first time empirically, that spatial-contextual (allocentric) memory ability is negatively associated with severity of intrusive memories in 33 patients with PTSD. The findings of the present work indicate that (1) dissociation in DPD is underpinned by different alterations in structural connectivity than in PTSD-D and (2) dissociative and intrusive memories are associated with aberrations in similar sub-cortical circuits, supporting the notion that in PTSD-D, a lower state of consciousness exacerbates de-contextualization of the traumatic content, resulting in heightened intrusive symptomatology. Clinical implications of our findings are discussed.
Keywords	Biological Neural Networks ; Biologische Neuronale Netze ; Brain ; Brain Connectivity ; Depersonalisation ; Depersonalisations-Derealisationsstörung ; Depersonalization ; Depersonalization/Derealization Disorder ; Dissociation ; Dissoziation ; Emotional Trauma ; Emotionales Trauma ; Gedächtnis ; Gehirn ; Intrusive Gedanken ; Intrusive Thoughts ; Konnektivität (Gehirn) ; Memory ; Mental Health ; Neurobiologie ; Neurobiology ; Posttraumatic Stress Disorder ; Posttraumatische Belastungsstörung ; Psychische Gesundheit ; Psychopathologie ; Psychopathology ; Symptome ; Symptoms ; Trauma ; Weiße Substanz (Gehirn) ; White Matter
Language	English
Size	82 pp., 87 pp. appendix
Publisher	Universität, Fachbereich Psychologie
Publishing place	Marburg
Document type	Book ; Thesis
Note	Elektronische Publikation im Internet. Kumulative Dissertation
DOI	10.17192/z2018.0512
Database	PSYNDEX

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Article: A pharmacological challenge paradigm to assess neural signatures of script-elicited acute dissociation in women with post-traumatic stress disorder.

Mertens, Yoki L / Manthey, Antje / Sierk, Anika / de Jong, Peter / Walter, Henrik / Daniels, Judith K

BJPsych open

2023 Volume 9, Issue 3, Page(s) e78

Abstract: Background: There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation.: Aims: To test the causal ... ...

Abstract	Background: There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation. Aims: To test the causal hypothesis that acute dissociation is triggered bottom-up by a selective noradrenergic-mediated increase in amygdala activation during the processing of autobiographical trauma memories. Method: Women with post-traumatic stress disorder ( Results: Self-reported acute dissociation increased significantly during trauma (versus neutral) recall but did not differ between pharmacological conditions. The pharmacological manipulation was also unsuccessful in eliciting increased amygdala activation following script-driven imagery in the reboxetine (versus placebo) condition. In the reboxetine condition, trauma retrieval resulted in similar activation patterns as in the placebo condition (e.g. elevated brain activation in the middle occipital gyrus and supramarginal gyrus), albeit with different peaks. Conclusions: Current (null) findings cast doubt on the suggested role of the amygdala in subserving dissociative processing of trauma memories. Alternative pharmacological manipulation approaches (e.g. ketamine) and analysis techniques (e.g. event-related independent component analysis) might provide better insight into the spatiotemporal dynamics and network shifts involved in dissociative experiences and autobiographical trauma memory recall.
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2829557-2
ISSN	2056-4724
ISSN	2056-4724
DOI	10.1192/bjo.2023.34
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A New Digital Assessment of Mental Health and Well-being in the Workplace: Development and Validation of the Unmind Index.

Sierk, Anika / Travers, Eoin / Economides, Marcos / Loe, Bao Sheng / Sun, Luning / Bolton, Heather

JMIR mental health

2022 Volume 9, Issue 1, Page(s) e34103

Abstract: Background: Unmind is a workplace, digital, mental health platform with tools to help users track, maintain, and improve their mental health and well-being (MHWB). Psychological measurement plays a key role on this platform, providing users with ... ...

Abstract	Background: Unmind is a workplace, digital, mental health platform with tools to help users track, maintain, and improve their mental health and well-being (MHWB). Psychological measurement plays a key role on this platform, providing users with insights on their current MHWB, the ability to track it over time, and personalized recommendations, while providing employers with aggregate information about the MHWB of their workforce. Objective: Due to the limitations of existing measures for this purpose, we aimed to develop and validate a novel well-being index for digital use, to capture symptoms of common mental health problems and key aspects of positive well-being. Methods: In Study 1A, questionnaire items were generated by clinicians and screened for face validity. In Study 1B, these items were presented to a large sample (n=1104) of UK adults, and exploratory factor analysis was used to reduce the item pool and identify coherent subscales. In Study 2, the final measure was presented to a new nationally representative UK sample (n=976), along with a battery of existing measures, with 238 participants retaking the Umind Index after 1 week. The factor structure and measurement invariance of the Unmind Index was evaluated using confirmatory factor analysis, convergent and discriminant validity by estimating correlations with existing measures, and reliability by examining internal consistency and test-retest intraclass correlations. Results: Studies 1A and 1B yielded a 26-item measure with 7 subscales: Calmness, Connection, Coping, Happiness, Health, Fulfilment, and Sleep. Study 2 showed that the Unmind Index is fitted well by a second-order factor structure, where the 7 subscales all load onto an overall MHWB factor, and established measurement invariance by age and gender. Subscale and total scores correlate well with existing mental health measures and generally diverge from personality measures. Reliability was good or excellent across all subscales. Conclusions: The Unmind Index is a robust measure of MHWB that can help to identify target areas for intervention in nonclinical users of a mental health app. We argue that there is value in measuring mental ill health and mental well-being together, rather than treating them as separate constructs.
Language	English
Publishing date	2022-01-17
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2798262-2
ISSN	2368-7959
ISSN	2368-7959
DOI	10.2196/34103
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Article: Neural correlates of acute post-traumatic dissociation: a functional neuroimaging script-driven imagery study.

Mertens, Yoki L / Manthey, Antje / Sierk, Anika / Walter, Henrik / Daniels, Judith K

BJPsych open

2022 Volume 8, Issue 4, Page(s) e109

Abstract: Background: Current neurobiological models of post-traumatic stress disorder (PTSD) assume excessive medial frontal activation and hypoactivation of cortico-limbic regions as neural markers of post-traumatic dissociation. Script-driven imagery is an ... ...

Abstract	Background: Current neurobiological models of post-traumatic stress disorder (PTSD) assume excessive medial frontal activation and hypoactivation of cortico-limbic regions as neural markers of post-traumatic dissociation. Script-driven imagery is an established experimental paradigm that is used to study acute dissociative reactions during trauma exposure. However, there is a scarcity of experimental research investigating neural markers of dissociation; findings from existing script-driven neuroimaging studies are inconsistent and based on small sample sizes. Aims: The current aim was to identify the neural correlates of acute post-traumatic dissociation by employing the script-driven imagery paradigm in combination with functional magnetic resonance imaging. Method: Functional neuroimaging data was acquired in 51 female patients with PTSD with a history of interpersonal childhood trauma. Blood-oxygen-level-dependent response during the traumatic (versus neutral) autobiographical memory recall was analysed, and the derived activation clusters were correlated with dissociation measures. Results: During trauma recall, enhanced activation in the cerebellum, occipital gyri, supramarginal gyrus and amygdala was identified. None of the derived clusters correlated significantly with dissociative symptoms, although patients reported increased levels of acute dissociation following the paradigm. Conclusions: The present study is one of the largest functional magnetic resonance imaging investigations of dissociative neural biomarkers in patients with PTSD undergoing experimentally induced trauma confrontation to elicit symptom-specific brain reactivity. In light of the current reproducibility crisis prominent in neuroimaging research owing to costly and time-consuming data acquisition, the current (null) findings highlight the difficulty of extracting reliable neurobiological biomarkers for complex subjective experiences such as dissociation.
Language	English
Publishing date	2022-06-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2829557-2
ISSN	2056-4724
ISSN	2056-4724
DOI	10.1192/bjo.2022.65
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Article: Does trauma-focused psychotherapy change the brain? A systematic review of neural correlates of therapeutic gains in PTSD.

Manthey, Antje / Sierk, Anika / Brakemeier, Eva-Lotta / Walter, Henrik / Daniels, Judith K

European journal of psychotraumatology

2021 Volume 12, Issue 1, Page(s) 1929025

Abstract: Background: Meta-analytic results indicate that posttraumatic stress disorder (PTSD) is associated with hypoactivation of the medial prefrontal cortex (mPFC), hyperactivation of the amygdala, and volume reductions of the hippocampus. Effective ... ...

Abstract	Background: Meta-analytic results indicate that posttraumatic stress disorder (PTSD) is associated with hypoactivation of the medial prefrontal cortex (mPFC), hyperactivation of the amygdala, and volume reductions of the hippocampus. Effective psychotherapeutic treatments were hypothesized to normalize these neural patterns via upregulation of prefrontal structures, which in turn downregulate limbic regions. Objective: To gain a sound understanding of the effects of successful psychotherapy on the brain, neural changes from pre- to post-treatment in PTSD patients will be aggregated. Method: A systematic literature search identified 24 original studies employing structural or functional MRI measurements both before and after treatment of patients diagnosed with PTSD. Results: In conjunction, the review returned little evidence of an activation increase in the mPFC/rostral anterior cingulate cortex (rACC) following successful treatment. Five out of 12 studies observed such an increase (especially during emotion processing tasks), albeit in partially non-overlapping brain regions. Conversely, neither the putative related activation decrease in the amygdala nor volumetric changes or altered activation during the resting state could be convincingly established. Conclusion: Successful psychological treatments might potentially work via upregulation of the mPFC, which thus may be involved in symptom reduction. However, the role of the amygdala in recovery from PTSD remains unclear. There is currently no indication that the various PTSD treatment approaches employed by the reviewed studies differ regarding their action mechanisms, but further research on this topic is needed.
MeSH term(s)	Amygdala/physiopathology ; Brain/physiopathology ; Brain Mapping ; Gyrus Cinguli/physiopathology ; Hippocampus/physiopathology ; Humans ; Prefrontal Cortex/physiopathology ; Psychotherapy ; Stress Disorders, Post-Traumatic/physiopathology
Language	English
Publishing date	2021-08-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2586642-4
ISSN	2000-8066
ISSN	2000-8066
DOI	10.1080/20008198.2021.1929025
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Book ; Online ; Thesis: Neurobiological Underpinnings of Trauma-related Psychopathology

Sierk, Anika [Verfasser] / Brakemeier, Eva-Lotta [Akademischer Betreuer]

2019

Author's details	Anika Sierk ; Betreuer: Eva-Lotta Brakemeier
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Philipps-Universität Marburg
Publishing place	Marburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: The dissociative subtype of posttraumatic stress disorder is associated with subcortical white matter network alterations

Sierk, Anika / Manthey, Antje / Brakemeier, Eva-Lotta / Walter, Henrik / Daniels, Judith K.

Brain Imaging and Behavior

2021 Volume 15, Issue 2, Page(s) 643–655

Abstract: Posttraumatic stress disorder (PTSD) is characterized by intrusions, avoidance, and hyperarousal while patients of the dissociative subtype (PTSD-D) experience additional dissociative symptoms. A neurobiological model proposes hyper-inhibition of limbic ... ...

Title translation	Der dissoziative Subtyp der posttraumatischen Belastungsstörung hängt mit subkortikalen Netzwerkveränderungen der weißen Substanz zusammen
Abstract	Posttraumatic stress disorder (PTSD) is characterized by intrusions, avoidance, and hyperarousal while patients of the dissociative subtype (PTSD-D) experience additional dissociative symptoms. A neurobiological model proposes hyper-inhibition of limbic structures mediated by prefrontal cortices to underlie dissociation in PTSD. Here, we tested whether functional alterations in fronto-limbic circuits are underpinned by white matter network abnormalities on a network level. 23 women with PTSD-D and 19 women with classic PTSD participated. We employed deterministic diffusion tractography and graph theoretical analyses. Mean fractional anisotropy (FA) was chosen as a network weight and group differences assessed using network-based statistics. No significant white matter network alterations comprising both frontal and limbic structures in PTSD-D relative to classic PTSD were found. A subsequent whole brain exploratory analysis revealed relative FA alterations in PTSD-D in two subcortical networks, comprising connections between the left amygdala, hippocampus, and thalamus as well as links between the left ventral diencephalon, putamen, and pallidum, respectively. Dissociative symptom severity in the PTSD-D group correlated with FA values within both networks. Our findings suggest fronto-limbic inhibition in PTSD-D may present a dynamic neural process, which is not hard-wired via white matter tracts. Our exploratory results point towards altered fiber tract communication in a limbic-thalamic circuit, which may underlie (a) an initial strong emotional reaction to trauma reminders before conscious regulatory processes are enabled and (b) deficits in early sensory processing. In addition, aberrant structural connectivity in low-level motor regions may present neural correlates for dissociation as a passive threat-response.
Keywords	Brain Connectivity ; Dissociative Disorders ; Dissoziative Störungen ; Konnektivität (Gehirn) ; Limbic System ; Limbisches System ; Neuroanatomie ; Neuroanatomy ; Posttraumatic Stress Disorder ; Posttraumatische Belastungsstörung ; Symptome ; Symptoms ; Weiße Substanz (Gehirn) ; White Matter
Language	English
Document type	Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-020-00274-x
Database	PSYNDEX

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Article: Does trauma-focused psychotherapy change the brain? A systematic review of neural correlates of therapeutic gains in PTSD

Manthey, Antje / Sierk, Anika / Brakemeier, Eva-Lotta / Walter, Henrik / Daniels, Judith K.

European Journal of Psychotraumatology

2021 Volume 12, Issue 1, Page(s) No

Title translation	Verändert eine traumafokussierte Psychotherapie das Gehirn? Eine systematische Überprüfung der neuronalen Korrelate der therapeutischen Erfolge bei PTBS. (DeepL)
Abstract	Background: Meta-analytic results indicate that posttraumatic stress disorder (PTSD) is associated with hypoactivation of the medial prefrontal cortex (mPFC), hyperactivation of the amygdala, and volume reductions of the hippocampus. Effective psychotherapeutic treatments were hypothesized to normalize these neural patterns via upregulation of prefrontal structures, which in turn downregulate limbic regions. Objective: To gain a sound understanding of the effects of successful psychotherapy on the brain, neural changes from pre- to post-treatment in PTSD patients will be aggregated. Method: A systematic literature search identified 24 original studies employing structural or functional MRI measurements both before and after treatment of patients diagnosed with PTSD. Results: In conjunction, the review returned little evidence of an activation increase in the mPFC/rostral anterior cingulate cortex (rACC) following successful treatment. Five out of 12 studies observed such an increase (especially during emotion processing tasks), albeit in partially non-overlapping brain regions. Conversely, neither the putative related activation decrease in the amygdala nor volumetric changes or altered activation during the resting state could be convincingly established. Conclusion: Successful psychological treatments might potentially work via upregulation of the mPFC, which thus may be involved in symptom reduction. However, the role of the amygdala in recovery from PTSD remains unclear. There is currently no indication that the various PTSD treatment approaches employed by the reviewed studies differ regarding their action mechanisms, but further research on this topic is needed.
Keywords	Amygdala ; Brain ; Functional Magnetic Resonance Imaging ; Funktionelle Magnetresonanztomographie ; Gehirn ; Hippocampus ; Hippokampus ; Posttraumatic Stress Disorder ; Posttraumatische Belastungsstörung ; Prefrontal Cortex ; Präfrontaler Kortex ; Psychotherapie ; Psychotherapy ; Trauma Treatment ; Traumabehandlung
Language	English
Document type	Article
ZDB-ID	2586642-4
ISSN	2000-8066 ; 2000-8198
ISSN (online)	2000-8066
ISSN	2000-8198
DOI	10.1080/20008198.2021.1929025
Database	PSYNDEX

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Article: Akute Belastungsreaktion und Posttraumatische Belastungsstörung

Sierk, Anika / Manthey, Antje / Daniels, Judith K.

(In: Eckhardt-Henn, Annegret; Spitzer, Carsten (Ed.), Dissoziative Bewusstseinsstörungen. Grundlagen, Klinik, Therapie (S. 385-400). Stuttgart: Schattauer)

2017

Abstract: Es wird angenommen, dass Dissoziation eine wesentliche Rolle sowohl bei der Entstehung als auch im Verlauf traumaassoziierter Störungen spielt. Vor diesem Hintergrund werden die Prävalenz und der mögliche Einfluss dissoziativer Symptome bei der Akuten ... ...

Title translation	Acute stress reaction and posttraumatic stress disorder
Series title	In: Eckhardt-Henn, Annegret; Spitzer, Carsten (Ed.), Dissoziative Bewusstseinsstörungen. Grundlagen, Klinik, Therapie (S. 385-400). Stuttgart: Schattauer
Abstract	Es wird angenommen, dass Dissoziation eine wesentliche Rolle sowohl bei der Entstehung als auch im Verlauf traumaassoziierter Störungen spielt. Vor diesem Hintergrund werden die Prävalenz und der mögliche Einfluss dissoziativer Symptome bei der Akuten Belastungsreaktion und bei der Posttraumatischen Belastungsstörung (PTBS) beschrieben. Der Fokus liegt auf den Grundmechanismen und Auswirkungen posttraumatischer bzw. persistierender Dissoziation im Rahmen dieser beiden Störungsbilder. Außerdem werden Implikationen für die klinische Praxis behandelt. Für unerlässlich gehalten wird es, dass Dissoziation im Rahmen von Traumafolgestörungen nicht nur adäquat, sondern auch frühzeitig diagnostiziert wird. Einige Aspekte zum Umgang mit dissoziativen Symptomen sowie der Behandlung werden kurz skizziert. Es wird betont, dass die Befundlage insgesamt darauf hindeutet, dass Expositionstherapien auch für PTBS-Patienten mit dissoziativer Symptomatik profitabel sein können. Für die Chance auf eine vollständige Remission erscheinen allerdings die Kombination aus verschiedenen Therapiebausteinen sowie der Zusatz von Emotionsregulationstechniken und kognitiven Strategien als erfolgversprechend.
Keywords	Acute Stress ; Acute Stress Disorder ; Akute Stressstörung ; Akuter Stress ; Dissociation ; Dissoziation ; Etiology ; Posttraumatic Stress Disorder ; Posttraumatische Belastungsstörung ; Psychodiagnosis ; Psychodiagnostik ; Therapie ; Treatment ; Ätiologie
Language	German
Document type	Article
Database	PSYNDEX

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Article ; Online: The dissociative subtype of posttraumatic stress disorder is associated with subcortical white matter network alterations.

Sierk, Anika / Manthey, Antje / Brakemeier, Eva-Lotta / Walter, Henrik / Daniels, Judith K

Brain imaging and behavior

2017 Volume 15, Issue 2, Page(s) 643–655

Abstract	Posttraumatic stress disorder (PTSD) is characterized by intrusions, avoidance, and hyperarousal while patients of the dissociative subtype (PTSD-D) experience additional dissociative symptoms. A neurobiological model proposes hyper-inhibition of limbic structures mediated by prefrontal cortices to underlie dissociation in PTSD. Here, we tested whether functional alterations in fronto-limbic circuits are underpinned by white matter network abnormalities on a network level. 23 women with PTSD-D and 19 women with classic PTSD participated. We employed deterministic diffusion tractography and graph theoretical analyses. Mean fractional anisotropy (FA) was chosen as a network weight and group differences assessed using network-based statistics. No significant white matter network alterations comprising both frontal and limbic structures in PTSD-D relative to classic PTSD were found. A subsequent whole brain exploratory analysis revealed relative FA alterations in PTSD-D in two subcortical networks, comprising connections between the left amygdala, hippocampus, and thalamus as well as links between the left ventral diencephalon, putamen, and pallidum, respectively. Dissociative symptom severity in the PTSD-D group correlated with FA values within both networks. Our findings suggest fronto-limbic inhibition in PTSD-D may present a dynamic neural process, which is not hard-wired via white matter tracts. Our exploratory results point towards altered fiber tract communication in a limbic-thalamic circuit, which may underlie (a) an initial strong emotional reaction to trauma reminders before conscious regulatory processes are enabled and (b) deficits in early sensory processing. In addition, aberrant structural connectivity in low-level motor regions may present neural correlates for dissociation as a passive threat-response.
MeSH term(s)	Diffusion Tensor Imaging ; Dissociative Disorders/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Stress Disorders, Post-Traumatic/diagnostic imaging ; White Matter/diagnostic imaging
Language	English
Publishing date	2017-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-020-00274-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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