The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD)

Bremner, J. Douglas; Hoffman, Matthew; Afzal, Nadeem; Cheema, Faiz A.; Novik, Olga; Ashraf, Ali; Nazeer, Ahsan; Goldberg, Jack; Vaccarino, Viola

doi:10.1016/j.jpsychires.2020.10.042

Cited by 27 publications

(16 citation statements)

References 143 publications

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“…An example for such non-linear effects on anxiety-phenotype is the Caffeinen-ADORA2A Genotype-Interaction (Childs et al 2008). In line with this, a recent structural imaging analysis in combat veterans suggest that changes in hippocampal volume can be primarily attributed to environmental factors, such as stress of combat (Bremner et al 2020). Taken together, further studies are needed to disentangle the magnitude of environmental and genetic involvement in traumatizing environments.…”

Section: Discussionmentioning

confidence: 90%

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort

Weber¹,

Maihofer

Jakšić

et al. 2021

J Neural Transm

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Objectives Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. Methods Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. Results The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. Conclusions The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.

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Section: Discussionmentioning

confidence: 90%

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort

Weber¹,

Maihofer

Jakšić

et al. 2021

J Neural Transm

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“…44 for civilian PTSD). There are avenues to further explore with regard to the hippocampus, including genotype, 45 combat stress, 46 and extended time since trauma 47 . In sum, larger subcortical regions observed in PTSD appear to be associated with adulthood and military trauma.…”

Section: Discussionmentioning

confidence: 99%

Whole‐brain morphometry in Canadian soldiers with posttraumatic stress disorder

Roy

Levasseur-Moreau

Renauld

et al. 2021

Annals of the New York Academy of Sciences

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Patients with posttraumatic stress disorder (PTSD) display several structural brain differences when compared with healthy individuals. However, findings are particularly inconsistent for soldiers with PTSD. Here, we characterized the brain morphometry of 37 soldiers from the Canadian Armed Forces with adulthood war‐related PTSD using structural magnetic resonance imaging. We assessed time since trauma, as well as PTSD, depressive, and anxiety symptoms with the Modified PTSD Symptoms Scale, Beck Depression Inventory, and Beck Anxiety Inventory, respectively. Whole‐brain morphometry was extracted with FreeSurfer and compared with a validated normative database of more than 2700 healthy individuals. Volume and thickness from several regions differed from the norms. Frontal regions were smaller and thinner, particularly the superior and rostral middle frontal gyri. Furthermore, smaller left rostral middle frontal gyrus, left pericalcarine cortex, and right fusiform gyrus were associated with more recent trauma. All subcortical structures were bigger, except the hippocampus. These findings suggest a particular brain morphometric signature of PTSD in soldiers. Smaller and thinner frontal and larger subcortical regions support impaired top‐down and/or downregulation of emotional response in PTSD. Finally, the correlation of smaller frontal, temporal, and occipital regions with more recent trauma might inform future therapeutic approaches.

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“…In fact, as we will review below, the data suggest that chronic and severe PTSD is linked with a disruption of the threat response system that can contribute to a blunting of this system. This is supported by multiple theoretical perspectives, including the glucocorticoid vulnerability hypothesis (Conrad, 2008), which predicts that prolonged stress inherent to chronic PTSD may result in hippocampus neuronal damage, which could then impair acute threat responses (Bach et al, 2014;Bremner et al, 2020). It is also possible that reduced hippocampal volume could yield overgeneralization of fear to previously neutral stimuli or contexts (Maren & Holt, 2000), thereby overwhelming the threat response system (McTeague & Lang, 2012) and yielding blunted threat responses in even simple association tasks (e.g., Katz et al, 2018;Lieberman et al, 2020;Medina et al, 2001).…”

Section: Theoretical Role Of Defensive Responding To External Threat ...mentioning

confidence: 99%

Diminished responses to external threat as a possible link between chronic/severe posttraumatic stress disorder and suicide.

Albanese¹,

Preston²,

Capron³

et al. 2021

Psychological Trauma: Theory, Research, Practice, and Policy

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Objective: Posttraumatic stress disorder (PTSD) is linked with suicide attempt history, but the neurobehavioral mechanisms explaining this association are unclear. The narrative review presented here proposes that blunted neurobehavioral responses to acute external threat represent one pathway via which chronic, severe, and/or multitrauma PTSD may increase risk for a suicide attempt among those with suicidal desire. Method: A brief review of theoretical perspectives on diminished responding to external threats in suicide and PTSD is provided (Part 1) followed by the presentation of existing evidence using neurophysiological (Part 2), startle reflex and autonomic (Part 3), and behavioral (Part 4) measures of threat reactivity among individuals with past suicide attempts and PTSD. Results: Findings generally support the proposal that blunted neurobehavioral responses to threat may link chronic and severe PTSD with suicide, though more evidence from all levels of analysis is needed. Additional questions also remain, including the relative influences of multiple traumatic events and PTSD severity as well as the directionality of the associations among PTSD, suicide, and blunted threat responses. Conclusions: Blunted neurobehavioral responses to external threats appear to be one plausible mechanism via which chronic, severe, and/or multitrauma PTSD may elevate risk for a suicide attempt when combined with suicidal desire. Future research should seek to use intensive longitudinal designs to evaluate the directionality of relations between PTSD, suicide, and threat reactivity across multiple levels of analysis, including the behavioral freeze response. Clinical Impact StatementThe present review proposes, and reviews evidence for, blunted responses to external threat as a plausible transdiagnostic risk factor linking posttraumatic stress disorder and suicide. This work may inform the development of targeted interventions to normalize threat responses in these populations.

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The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD)

Cited by 27 publications

References 143 publications

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort

Whole‐brain morphometry in Canadian soldiers with posttraumatic stress disorder

Diminished responses to external threat as a possible link between chronic/severe posttraumatic stress disorder and suicide.

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