Judith K. Daniels

WHITE MATTER INTEGRITY AND ITS RELATIONSHIP TO PTSD AND CHILDHOOD TRAUMA—A SYSTEMATIC REVIEW AND META-ANALYSIS

Recent reviews and meta‐analyses reported structural gray matter changes in patients suffering from adult‐onset posttraumatic stress disorder (PTSD) and in subjects with and without PTSD who experienced childhood trauma. However, it remains unclear if such structural changes are also affecting the white matter. The aim of this systematic review is to provide a comprehensive overview of all empirical investigations measuring white matter integrity in populations affected by PTSD and/or childhood trauma. To this end, results from different methodological approaches were included. Twenty‐five articles are reviewed of which 10 pertained to pediatric PTSD and the effects of childhood trauma measured during childhood, seven to the effects of childhood trauma measured during adulthood, and eight to adult‐onset PTSD. Overall, reductions in white matter volume were reported more often than increases in these populations. However, the heterogeneity of the exact locations indicates only a weak overlap across published studies. In addition, a meta‐analysis was carried out on seven whole‐brain diffusion tensor imaging (DTI) studies in adults. Significant clusters of both increases and decreases were identified in various structures, most notably the cingulum and the superior longitudinal fasciculus. Future research directions are discussed.

Effects of trauma-related cues on pain processing in posttraumatic stress disorder: an fMRI investigation.

BACKGROUND Imaging studies of pain processing in primary psychiatric disorders are just emerging. This study explored the neural correlates of stress-induced analgesia in individuals with posttraumatic stress disorder (PTSD). It combined functional magnetic resonance imaging (fMRI) and the traumatic script-driven imagery symptom provocation paradigm to examine the effects of trauma-related cues on pain perception in individuals with PTSD. METHODS The study included 17 patients with PTSD and 26 healthy, trauma-exposed controls. Participants received warm (nonpainful) or hot (painful) thermal stimuli after listening to a neutral or a traumatic script while they were undergoing an fMRI scan at a 4.0 T field strength. RESULTS Between-group analyses revealed that after exposure to the traumatic scripts, the blood oxygen level-dependent (BOLD) signal during pain perception was greater in the PTSD group than the control group in the head of the caudate. In the PTSD group, strong positive correlations resulted between BOLD signal and symptom severity in a number of brain regions previously implicated in stress-induced analgesia, such as the thalamus and the head of the caudate nucleus. Trait dissociation as measured by the Dissociative Experiences Scale correlated negatively with the right amygdala and the left putamen. LIMITATIONS This study included heterogeneous traumatic experiences, a different proportion of military trauma in the PTSD versus the control group and medicated patients with PTSD. CONCLUSION These data indicate that in patients with PTSD trauma recall will lead in a state-dependent manner to greater activation in brain regions implicated in stress-induced analgesia. Correlational analyses lend support to cortical hyperinhibition of the amygdala as a function of dissociation.

Alterations in Default Mode Network Connectivity During Pain Processing in Borderline Personality Disorder

CONTEXT Recent neuroimaging studies have associated activity in the default mode network (DMN) with self-referential and pain processing, both of which are altered in borderline personality disorder (BPD). In patients with BPD, antinociception has been linked to altered activity in brain regions involved in the cognitive and affective evaluation of pain. Findings in healthy subjects indicate that painful stimulation leads to blood oxygenation level-dependent signal decreases and changes in the functional architecture of the DMN. OBJECTIVES To connect the previously separate research areas of DMN connectivity and altered pain perception in BPD and to explore DMN connectivity during pain processing in patients with BPD. DESIGN Case-control study. SETTING University hospital. PARTICIPANTS Twenty-five women with BPD, including 23 (92%) with a history of self-harm, and 22 age-matched control subjects. INTERVENTIONS Psychophysical assessment and functional magnetic resonance imaging during painful heat vs neutral temperature stimulation. MAIN OUTCOME MEASURE Connectivity of DMN as assessed via independent component analysis and psychophysiological interaction analysis. RESULTS Compared with control subjects, patients with BPD showed less integration of the left retrosplenial cortex and left superior frontal gyrus into the DMN. Higher BPD symptom severity and trait dissociation were associated with an attenuated signal decrease of the DMN in response to painful stimulation. During pain vs neutral, patients with BPD exhibited less posterior cingulate cortex seed region connectivity with the left dorsolateral prefrontal cortex. CONCLUSIONS Patients with BPD showed significant alterations in DMN connectivity, with differences in spatial integrity and temporal characteristics. These alterations may reflect a different cognitive and affective appraisal of pain as less self-relevant and aversive as well as a deficiency in the switching between baseline and task-related processing. This deficiency may be related to everyday difficulties of patients with BPD in regulating their emotions, focusing mindfully on 1 task at a time, and efficiently shifting their attention from one task to another.

Default mode alterations in posttraumatic stress disorder related to early-life trauma: a developmental perspective

Recently, altered default mode network (DMN) connectivity in individuals with posttraumatic stress disorder (PTSD) has been related to prolonged childhood maltreatment.1 An emerging body of literature also describes the developmental differentiation of the DMN in healthy children.2–6 Critically, developmental changes in the DMN may parallel those observed in other associated domains, including self-referential processing, autobiographical memory, prospection and theory of mind, which are thought to rely on many of the same underlying processes and neural substrates implicated in the DMN.7 Moreover, deficient DMN connectivity in adults with childhood maltreatment–related PTSD appears similar to patterns of DMN connectivity observed in healthy children aged 7 to 9 years. Here, we propose that early-life trauma may interfere with the developmental trajectory of the DMN and its associated functions.8–11

Heart rate variability and its neural correlates during emotional face processing in social anxiety disorder

The monitoring and regulation of ones own physiological reactions and cardioregulatory abnormalities are central to the aetiology and maintenance of social anxiety disorder (SAD). We therefore explored the neural correspondences of these heart rate alterations. 21 patients with SAD and 21 matched healthy controls (HCs) underwent 3T-fMRI scanning. Simultaneously, high-frequency heart rate variability (HF-HRV) was acquired during a short-term resting period and an implicit emotional face-matching task. Compared to HCs, patients with SAD reported increased self-focused attention while being less accurate in estimating their heartbeats. Physiologically, they showed less HF-HRV at rest and during task. Across groups, HF-HRV at rest correlated positively with activation in visual face-processing areas. The right caudate nucleus showed an interaction of group and cardioregulation: Activation in this region was positively correlated in patients with SAD but negatively in HCs. We conclude that cardioregulation is altered in SAD on the subjective, physiological, and brain level.

German Screen for Child Anxiety Related Emotional Disorders (SCARED): Reliability, Validity, and Cross-Informant Agreement in a Clinical Sample

BackgroundThe psychometric properties and cross-informant agreement of a German translation of the Screen for Child Anxiety Related Emotional Disorders (SCARED) were assessed in a clinical sampleMethods102 children and adolescents in outpatient psychotherapy and their parents filled out the SCARED and Youth Self Report/Child Behaviour Checklist (YSR/CBCL).ResultsThe German SCARED showed good internal consistency for both parent and self-report version, and proved to be convergently and discriminantly valid when compared with YSR/CBCL scales. Cross-informant agreement was moderate with children reporting both a larger number as well as higher severity of anxiety symptoms than their parents.ConclusionIn conclusion, the German SCARED is a valid and reliable anxiety scale and may be used in a clinical setting

Intrinsic Connectivity Networks in post-traumatic stress disorder during sub- and supraliminal processing of threat-related stimuli

To investigate the functional connectivity of large‐scale intrinsic connectivity networks (ICNs) in post‐traumatic stress disorder (PTSD) during subliminal and supraliminal presentation of threat‐related stimuli.

Neural correlates and predictive power of trait resilience in an acutely traumatized sample: a pilot investigation.

OBJECTIVE Resilience refers to the ability to thrive despite adversity and is defined as a multidimensional phenomenon, spanning internal locus of control, sense of meaning, social problem-solving skills, and self-esteem. We aimed to investigate the predictive value of resilience for the development of posttraumatic stress disorder (PTSD) and to examine the neural correlates mediating the relationship between resilience and recovery from a traumatic event in acutely traumatized subjects. We hypothesized that resilience would mediate the relationship between childhood trauma and posttraumatic recovery. METHOD We conducted a prospective study with 70 acutely traumatized subjects with DSM-IV PTSD recruited at the emergency department, assessing PTSD symptom severity at 3 time points within the first 3 months posttrauma. Scores for childhood trauma as assessed with the Childhood Trauma Questionnaire and trait resilience as assessed with the Connor-Davidson Resilience Scale were used as predictors of symptom severity. A subsample of 12 subjects additionally underwent a functional 4 Tesla magnetic resonance imaging scan 2 to 4 months posttrauma. We employed the traumatic script-driven imagery paradigm to assess the correlations between trait resilience and blood oxygen level-dependent (BOLD) response. The study was conducted from 2003 to 2007. RESULTS Resilience predicted PTSD symptom severity at 5 to 6 weeks (β = -0.326, P = .01) as well as at 3 months (β = -0.423, P = .003) posttrauma better than childhood trauma. Resilience essentially mediated the relationship between childhood trauma and posttraumatic adjustment. Resilience scores were positively correlated with BOLD signal strength in the right thalamus as well as the inferior and middle frontal gyri (Brodmann area 47). CONCLUSIONS This pilot investigation revealed a significant relationship between resilience and emotion regulation areas during trauma recall in an acutely traumatized sample. Resilience was established as a significant predictor of PTSD symptom severity and mediated the influence of childhood trauma on posttraumatic adjustment.

Neural and behavioral correlates of peritraumatic dissociation in an acutely traumatized sample.

OBJECTIVE Peritraumatic dissociative responses have been identified as strong predictors of subsequent posttraumatic stress disorder development. We aimed to clarify the mechanism by which peritraumatic dissociation is related to PTSD development by exploring the neural correlates of peritraumatic dissociation during posttraumatic adjustment. METHOD We combined a prospective questionnaire study with a neuroimaging paradigm in an acutely traumatized sample recruited from the emergency department from 2004 until 2009. 121 acutely traumatized subjects were assessed for acute stress disorder, PTSD, and dissociative symptoms at 3 time points within the first 3 months post trauma. A subsample of 21 subjects underwent a script-driven 4-Tesla functional magnetic resonance imaging scan 2 to 4 months post trauma. RESULTS Peritraumatic dissociation predicted PTSD diagnostic status at 5-6 weeks and 3 months over and above childhood trauma (Wald = 4.035, P = .045; Wald = 4.793, P = .029, respectively). Peritraumatic dissociation scores were positively correlated with activation in the right occipital lobe, ie, the lingual (Brodmann area [BA] 18, z = 3.37), fusiform (BA 19, z = 3.64), and parahippocampal (BA 19, z = 3.25) gyri. After covariation of dissociation at the time of the scan, peritraumatic dissociation remained positively correlated with activation in the right lingual (BA 18, z = 3.21) and fusiform (BA 19, z = 3.55) gyri. CONCLUSIONS The neuroimaging findings indicate that peritraumatic dissociation is associated with greater activation of the right occipital lobe (BAs 18 and 19), a region previously implicated in vivid autobiographical memory recall of highly emotional events. These results suggest that peritraumatic dissociation directly leads to the formation of intrusive memories. Peritraumatic dissociation and childhood trauma emerged as valuable predictors of PTSD development and therefore can guide the identification of individuals at risk.

Effect of direct eye contact in women with PTSD related to interpersonal trauma: Psychophysiological interaction analysis of connectivity of an innate alarm system

In healthy individuals, direct eye contact is thought to modulate a cortical route eliciting social cognitive processes via activation of a fast subcortical pathway. This study aimed to examine functional brain connectivity during direct eye contact in women with posttraumatic stress disorder (PTSD) related to childhood abuse as compared with healthy controls. We conducted psychophysiological interaction (PPI) analyses in Statistical Parametric Mapping-8 (SPM8) using the superior colliculus (SC) and locus coeruleus (LC) as seed regions while 16 healthy subjects and 16 patients with a primary diagnosis of PTSD related to childhood maltreatment viewed a functional magnetic resonance imaging (fMRI) paradigm involving direct (D) versus averted (A) gaze (happy, sad, neutral). The PTSD group showed a significantly enhanced connectivity between the SC and the anterior cingulate, and between the LC and the thalamus, caudate, putamen, insula, cingulate gyrus, and amygdala, as compared with healthy individuals. Symptom severity scores on the Clinician-Administered PTSD Scale (CAPS) showed significant positive correlations with superior colliculus connectivity with the perigenual and posterior cingulate, insula, and sublenticular extended amygdala. Functional connectivity data suggest increased recruitment of brain regions involved in emotion processing during direct gaze in PTSD in association with the fast subcortical pathway. The interpretation of eye contact as a signal of threat may require more emotion regulatory capacities in patients with PTSD.