Structural Neuroimaging of Hippocampus and Amygdala Subregions in Posttraumatic Stress Disorder: A Scoping Review.

Numerous studies have explored the relationship between posttraumatic stress disorder (PTSD) and the hippocampus and the amygdala because both regions are implicated in the disorder's pathogenesis and pathophysiology. Nevertheless, those key limbic regions consist of functionally and cytoarchitecturally distinct substructures that may play different roles in the etiology of PTSD. Spurred by the availability of automatic segmentation software, structural neuroimaging studies of human hippocampal and amygdala subregions have proliferated in recent years. Here, we present a preregistered scoping review of the existing structural neuroimaging studies of the hippocampus and amygdala subregions in adults diagnosed with PTSD. A total of 3513 studies assessing subregion volumes were identified, 1689 of which were screened, and 21 studies were eligible for this review (total N = 2876 individuals). Most studies examined hippocampal subregions and reported decreased CA1, CA3, dentate gyrus, and subiculum volumes in PTSD. Fewer studies investigated amygdala subregions and reported altered lateral, basal, and central nuclei volumes in PTSD. This review further highlights the conceptual and methodological limitations of the current literature and identifies future directions to increase understanding of the distinct roles of hippocampal and amygdalar subregions in posttraumatic psychopathology.

Acute dissociation as part of the defense cascade: Associations with behavioral, autonomic, and experiential threat responses in posttraumatic stress disorder.

Dissociative symptoms, such as depersonalization and derealization, are experienced by about half of individuals with posttraumatic stress disorder (PTSD). Theoretical models propose that acute dissociation is accompanied by specific behavioral, physiological, and experiential alterations and contributes to unfavorable PTSD symptom course. Yet, empirical evidence is scarce. Here, we explored associations between dissociative and behavioral, physiological, and experiential threat responses as well as effects of dissociative responding on PTSD symptom course. Individuals with PTSD (N = 71) participated in a preregistered script-driven imagery study including exposure to standardized, detail-enriched trauma, and neutral scripts. Stabilometry, eye-tracking, facial electromyography, autonomic psychophysiology, and self-report data were collected. Moreover, PTSD symptoms were assessed before and 3 months after testing. Analyses did not link acute dissociation to bodily and facial immobility or staring in response to trauma scripts. However, dissociation displayed an inverted U-shaped relationship with heart rate and was linked to higher nonspecific skin conductance fluctuation and higher high-frequency heart rate variability in response to trauma scripts. Moreover, acute dissociation was linked to higher self-reported negative affect responses to trauma scripts and displayed a U-shaped relationship with unfavorable PTSD symptom course. While results did not confirm hypothesized behavioral markers of dissociation, they do support defense-cascade model assumptions of an inverted U-shaped relationship between dissociation and psychophysiological arousal resulting from a progression of parasympathetic versus sympathetic dominance with increasing dissociation. On an experiential level, results did not confirm posttraumatic dissociation-induced emotional numbing, questioning theoretical notions. The observed nonlinear associations may help explain the heterogeneity of prior findings and might inform an updated conceptualization of posttraumatic dissociation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study.

RATIONALE: A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking. OBJECTIVES: The present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD. METHODS: Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion. RESULTS: Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam. CONCLUSIONS: A dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.

Psychometric properties of the dissociative subtype of posttraumatic stress disorder scale: replication and extension in two German-speaking samples.

Background: The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced the dissociative subtype of posttraumatic stress disorder (D-PTSD). To assess this subtype, the Dissociative Subtype of PTSD Scale (DSPS), a 15-item self-report measure to identify lifetime and current dissociative symptoms of D-PTSD, was developed. However, so far, the scale has only been validated in war veterans. Moreover, criterion validity and diagnostic utility have not been examined yet.Objective: We aimed to validate the DSPS in two samples of civilian trauma-exposed German-speaking participants.Methods: In Study 1, a pre-registered online study, participants with and without PTSD symptoms (N = 558) answered questionnaires about traumatic experiences, dissociation, PTSD, depression, generalized anxiety disorder, somatic symptom disorder, alcohol use disorder, absorption, and dissociative responding to trauma-related questionnaires. In Study 2, which used secondary data of a pre-registered clinical study, participants with a PTSD diagnosis (N = 71) answered questionnaires about traumatic experiences, dissociation, PTSD, depression, generalized anxiety disorder, somatic symptom disorder, and dissociative responding to standardized trauma exposure. Moreover, PTSD, D-PTSD, and other diagnoses were assessed with structured clinical interviews.Results: Analyses confirmed a three-factor structure as well as high internal consistency, and high convergent, discriminant, and criterion validity of the DSPS. Moreover, the scale was able to identify a latent D-PTSD group and individuals with D-PTSD diagnosis.Conclusions: The DSPS constitutes a reliable and valid tool to assess D-PTSD symptoms in clinical practice and research and thereby may contribute to a better understanding of these debilitating symptoms.

Many individuals with posttraumatic stress disorder (PTSD) suffer from dissociative symptoms which can be assessed with the Dissociative Subtype of PTSD Scale (DSPS; Wolf et al., 2017).The DSPS demonstrated good psychometric properties in two German-speaking trauma-exposed samples and hence might be used to assess D-PTSD symptoms in research and clinical practice.Complementing the original English version, a German version of the DSPS is provided in the Supplements.

Experimental induction of peritraumatic dissociation: The role of negative affect and pain and their psychophysiological and neural correlates.

While research has elucidated processes underlying dissociative symptoms in patients with posttraumatic stress disorder, little is known about the circumstances under which trauma-related dissociation initially arises. To experimentally investigate causes and concomitants of peritraumatic dissociation, we subjected sixty-nine healthy women to aversive-audiovisual and painful-electrical stimulation in a 2(aversive/neutral film) x 2(pain/no pain) within-subject design while recording psychophysiological and fMRI-BOLD responses. Afterwards, participants rated negative-affect, pain, and dissociation for each condition. Using Bayesian multilevel regression models, we examined (1) whether aversive-audiovisual and painful-electrical stimulation elicit higher dissociation-levels than control conditions and (2) whether stronger negative-affect and pain responses (operationalized via self-report, psychophysiological, and neural markers) correlate with higher dissociation-levels. Several key findings emerged: Both aversive-audiovisual and painful-electrical stimulation elicited dissociation. Dissociation was linked to higher self-reported negative-affect, but we did not find enough evidence linking it to psychophysiological and neural negative-affect markers. However, dissociation was associated with higher levels of self-reported pain, a skin-conductance-response-based pain marker, and the fMRI-BOLD-based Neurologic-Pain-Signature. Results indicate that both aversive-audiovisual and painful stimuli can independently cause dissociation. Critically, pain responses captured via self-report, psychophysiological, and neural markers were consistently linked to higher dissociation-levels suggesting a specific, evolutionary meaningful, contribution of pain to the rise of dissociation.

Estradiol during (analogue-)trauma: Risk- or protective factor for intrusive re-experiencing?

Intrusions, a key symptom of posttraumatic stress disorder (PTSD), can occur in the form of images but also as pain sensations. Similar to audiovisual intrusions, the frequency and persistence of pain intrusions varies greatly between individuals. In the current study, we examined whether peritraumatic circulating 17ß-estradiol (E2) levels are a biologic factor associated with subsequent audiovisual (i.e., film) and pain intrusion development, and whether peritraumatic stress levels modulate this relationship. Forty-one free-cycling women participated in an ecologically informed trauma-pain-conditioning (TPC) paradigm, using trauma-films and pain as unconditioned stimuli. Independent variables were salivary peritraumatic E2 levels and stress indexed by salivary cortisol and self-reported state-anxiety during TPC. Outcomes were film- and pain-intrusions occurring during daily-life in the week following TPC and a Memory-Triggering-Task in response to conditioned stimuli 24 h after TPC. In the week after analogue-trauma, higher peritraumatic E2 levels were associated with a greater probability of experiencing film-intrusions in the beginning of the week, which switched to a lower probability toward the end of the week. This time-dependent relationship between E2 and film-intrusions only held for higher state-anxious women. In contrast, results indicated a consistent inverse relationship between peritraumatic E2 levels and pain-intrusions during daily-life and Memory-Triggering-Task. Together, these data suggest that higher peritraumatic E2 levels could be associated with lower long-term visual trauma intrusions, as well as lower pain-intrusions, and thereby possibly constitute a protective biologic factor for PTSD and potentially also for chronic pain.

Neuroscientific evidence for pain being a classically conditioned response to trauma- and pain-related cues in humans.

ABSTRACT: Psychological trauma is typically accompanied by physical pain, and posttraumatic stress disorder (PTSD) often cooccurs with chronic pain. Clinical reports suggest that pain after trauma may be part of re-experiencing symptomatology. Classical conditioning can underlie visual re-experiencing because intrusions can occur as conditioned responses (CRs) to trauma-related cues. If individuals also experience pain to cues previously paired with, but not inflicting nociceptive stimulation anymore (ie, conditioned stimuli, CS), conditioning could also explain re-experiencing of pain. Sixty-five participants underwent classical conditioning, where painful electrocutaneous stimulation and aversive film clips served as unconditioned stimuli (US) in a 2 (pain/no pain) × 2 (aversive/neutral film) design. Conditioned stimuli were neutral pictures depicting contextual details from the films. One day later, participants were re-exposed to CS during a memory-triggering task (MTT). We assessed pain-CRs by self-report and an fMRI-based marker of nociceptive pain, the neurological pain signature (NPS), and recorded spontaneous daily-life pain intrusions with an e-diary. During conditioning, pain-signaling CS elicited more self-reported pain and NPS responses than no-pain-signaling CS. Possibly because the aversive film masked differences in participants' responses to pain-signaling CS vs no pain-signaling CS, pain-CRs during acquisition were most evident within the neutral film condition. When participants were re-exposed to CS during MTT, self-reported pain-CRs during the neutral film condition and, although more uncertain, NPS-CRs during the aversive film condition persisted. Of importance, participants with stronger pain-CRs showed a greater probability and severity of experiencing spontaneous pain intrusions during daily life. Our data support that spatiotemporally associating innocuous cues with pain (CS) endows these cues to elicit conditioned pain responses in the absence of noxious stimulation. In this way pain can emerge as a CR with emotional and sensory components. Classical conditioning presents a possible mechanism explaining pain intrusions and, more broadly, pain experienced without a nociceptive input.

Peritraumatic dissociation revisited: associations with autonomic activation, facial movements, staring, and intrusion formation.

Background: Peritraumatic dissociation is purported to emerge together with attenuated autonomic arousal, immobility, and staring. However, empirical evidence is scarce and heterogeneous. Moreover, it is still a matter of debate whether these responses predict intrusion formation. Objective: The present trauma-analogue study examined associations between peritraumatic dissociation, autonomic activation, facial movements, staring, and intrusion formation. Method: Seventy-one healthy women watched a highly aversive film, while autonomic activation (heart rate, respiratory sinus arrhythmia, skin conductance level), facial movements (temporal variations in corrugator electromyography), and staring (fixation duration, tracklength) were assessed. Afterwards, participants rated the intensity of dissociation during film viewing and reported intrusions and associated distress in a smartphone application for 24 hours. Results: Peritraumatic dissociation was linked to higher autonomic arousal (higher heart rate and, on a trend-level, lower respiratory sinus arrhythmia), increased facial movements, and staring (lower tracklength). Peritraumatic dissociation, higher autonomic arousal (higher heart rate and lower respiratory sinus arrhythmia), staring (higher fixation duration), and, on a trend-level, more facial movements were linked to higher intrusion load (number x distress of intrusions) and together explained 59% of variance. Skin conductance level was neither linked to peritraumatic dissociation nor intrusion load. Conclusions: Our results suggest that, at low-dissociation-levels observed in trauma-analogue studies, peritraumatic dissociation may occur together with heightened autonomic arousal and facial movements, indexing increased negative affect. Staring might, irrespectively of dissociation-levels, serve as objective marker for dissociation. Together, peritraumatic dissociation and its psychophysiological correlates might set the stage for later intrusion formation.

Antecedentes: Se supone que la disociación peritraumática surge junto con la activación autonómica atenuada, la inmovilidad y la mirada fija. Sin embargo, la evidencia empírica es escasa y heterogénea. Además, sigue siendo objeto de debate si estas respuestas predicen la formación de intrusiones.Objetivo: El presente estudio análogo al trauma examinó las asociaciones entre la disociación peritraumática, la activación autonómica, los movimientos faciales, la mirada fija y la formación de intrusiones.Método: Setenta y una mujeres sanas vieron una película altamente aversiva mientras se evaluaba la activación autonómica (frecuencia cardíaca, arritmia sinusal respiratoria, nivel de conductancia de la piel), los movimientos faciales (variaciones temporales en la electromiografía del corrugador) y la mirada fija (duración de la fijación, longitud del seguimiento). Posteriormente, las participantes calificaron la intensidad de la disociación durante la visualización de la película e informaron sobre las intrusiones y la angustia asociada en una aplicación para teléfonos inteligentes durante 24 horas.Resultados: La disociación peritraumática se relacionó con una mayor activación autonómica (mayor frecuencia cardíaca y, a nivel de tendencia, menor arritmia sinusal respiratoria), mayores movimientos faciales y mirada fija (menor duración del seguimiento). La disociación peritraumática, la mayor activación autonómica (mayor frecuencia cardíaca y menor arritmia sinusal respiratoria), la mirada fija (mayor duración de la fijación) y, en un nivel de tendencia, más movimientos faciales estaban vinculados a una mayor carga de intrusiones (número x angustia de intrusiones) y juntos explicaban el 59% de la varianza. El nivel de conductancia de la piel no se relacionó con la disociación peritraumática ni con la carga de intrusión.Conclusiones: Nuestros resultados sugieren que, a niveles bajos de disociación observados en estudios de trauma análogos, la disociación peritraumática puede ocurrir junto con una mayor activación autonómica y movimientos faciales, lo que indica un aumento del afecto negativo. La mirada fija, independientemente de los niveles de disociación, podría servir como marcador objetivo de disociación. En conjunto, la disociación peritraumática y sus correlatos psicofisiológicos podrían sentar las bases para la formación posterior de intrusiones.

Intrusive memories as conditioned responses to trauma cues: An empirically supported concept?

Intrusions in posttraumatic stress disorder (PTSD) are clinically understood as conditioned responses (CRs) to trauma-cues; however, experimental evidence for this is limited. We subjected 84 healthy participants to a differential conditioned-intrusion paradigm, where neutral faces served as conditioned stimuli (CSs) and aversive film clips as unconditioned stimuli (USs). While one group only completed acquisition, another group additionally received extinction. Subsequently, participants provided detailed e-diary intrusion reports. Several key findings emerged: First, participants in both groups re-experienced not only USs but also CSs as content of their intrusions. Second, intrusions were elicited by cues resembling CSs, USs, and experimental context. Third, extinction reduced probability and severity of US intrusions, and accelerated their decay, and this was particularly the case in participants showing greater cognitive (US-expectancy) and physiological (SCR) differential responding to CS+ vs. CS- at end of acquisition (i.e., conditionability). Similarly, extinction reduced CS-intrusion probability and severity, but only in participants with greater cognitive conditionability. These results support conditioning's role in re-experiencing in two critical ways: (1) Conditioning during trauma provides cues that not only function as reminder cues, but also as content of intrusions; (2) After strong conditioning, weakening the original CS-US relationship via extinction reduces intrusion formation after analogue-trauma.

Pre-Sleep Arousal and Fear of Sleep in Trauma-Related Sleep Disturbances: A Cluster-Analytic Approach.

Background: Trauma-related sleep disturbances constitute critical symptoms of posttraumatic stress disorder (PTSD), but sleep symptoms often reside even after successful trauma-focused psychotherapy. Therefore, currently unattended factors - like fear of sleep (FoS) - might play a crucial role in the development and maintenance of residual sleep disturbances. However, it is unclear whether trauma-exposed individuals exhibit different symptomatic profiles of sleep disturbances that could inform individualized therapeutic approaches and eventually enhance treatment efficacy. Method: In a large online study, a two-step cluster analysis and a hierarchical cluster analysis using Ward's method were performed to explore subgroups among trauma-exposed individuals (N = 471) in terms of FoS, different aspects of trauma-related sleep disturbances (e.g., insomnia symptoms, nightmares, arousal), and PTSD symptoms. These variables were compared between resulting clusters using ANOVAs and Scheffé's post-hoc tests. Results: The hierarchical cluster analysis supported 3- and 4-cluster solutions. The 3-cluster solution consisted of one "healthy" (n = 199), one "subclinical" (n = 223), and one "clinical" (n = 49) cluster, with overall low, medium, and high symptomatology on all used variables. In the 4-cluster solution, the clinical cluster was further divided into two subgroups (n = 38, n = 11), where one cluster was specifically characterized by elevated somatic pre-sleep arousal and high levels of FoS. Conclusions: A subgroup of trauma-exposed individuals with PTSD and sleep disturbances suffers from increased pre-sleep arousal and FoS, which has been suggested as one possible explanation for residual sleep disturbances. In these patients, FoS might be a relevant treatment target.

Cardiac Vagal Control, Regulatory Processes and Depressive Symptoms: Re-Investigating the Moderating Role of Sleep Quality.

Lower cardiac vagal control (CVC), which is often understood as an indicator for impaired regulatory processes, is assumed to predict the development of depressive symptoms. As this link has not been consistently demonstrated, sleep quality has been proposed as a moderating factor. However, previous studies were limited by non-representative samples, cross-sectional data, and focused on CVC as a physiological indicator for impaired regulatory processes, but neglected corresponding subjective measures. Therefore, we investigated whether sleep quality moderates the effects of CVC (quantified by high-frequency heart rate variability) and self-reported regulatory processes (self- and emotion-regulation) on concurrent depressive symptoms and on depressive symptoms after three months in a representative sample (N = 125). Significant interactions between CVC and sleep quality (in women only), as well as self-/emotion-regulation and sleep quality emerged, whereby higher sleep quality attenuated the relation between all risk factors and current depressive symptoms (cross-sectional data). However, there were no significant interactions between those variables in predicting depressive symptoms three months later (longitudinal data). Our cross-sectional findings extend previous findings on sleep quality as a protective factor against depressive symptoms in the presence of lower CVC and subjective indices of impaired regulatory processes. In contrast, our conflicting longitudinal results stress the need for further investigations.

Out of the dark, into the light: The impact of social exclusion on judgments of darkness and brightness.

Based on theories of grounded cognition, we assumed that the experience of social exclusion is grounded in a concept of darkness. Specifically, we hypothesized that social exclusion causes perceptual judgments of darkness and a preference for brightness as a compensatory response. To investigate these hypotheses, we conducted four studies using different manipulations and measurements. In Studies 1a and 1b, excluded participants judged a picturized room as darker and drew more attention to its brightest part than included participants. In Study 2, excluded participants judged a surface as darker and decided for brighter clothing than included participants. In Study 3, excluded participants judged their lab room as darker and expressed a higher preference for brightness than included participants. Providing consistent support for our hypotheses, these findings confirm the idea that the experience of social exclusion is grounded in multiple ways that share a common representational system.