Kathleen Thomaes

Reduced anterior cingulate and orbitofrontal volumes in child abuse-related complex PTSD

OBJECTIVE Classic posttraumatic stress disorder (PTSD) is associated with smaller hippocampus, amygdala, and anterior cingulate cortex (ACC) volumes. We investigated whether child abuse-related complex PTSD--a severe form of PTSD with affect dysregulation and high comorbidity--showed similar brain volume reductions. METHOD We used voxel-based morphometry to measure gray matter concentrations in referred outpatients with child abuse-related complex PTSD (n = 31) compared to matched healthy nontraumatized controls (n = 28). Complex PTSD was diagnosed using the Structured Clinical Interview for DSM-IV-TR and the Structured Clinical Interview for Disorders of Extreme Stress. All respondents were scanned on a 1.5-T magnetic resonance system at the VU Medical Center, Amsterdam, The Netherlands, between September 2005 and February 2006. RESULTS As was hypothesized, patients with child abuse-related complex PTSD showed reductions in gray matter concentration in right hippocampus (P(SVC corrected) = .04) and right dorsal ACC (P(SVC corrected) = .02) compared to controls. In addition, a reduction in gray matter concentration in the right orbitofrontal cortex (OFC) was found. Severity of child abuse and PTSD-hyperarousal correlated negatively with ACC volume. Impulsivity correlated negatively with hippocampus volume, and anger, with hippocampus and OFC volume. Comorbidity of borderline personality disorder--compared to comorbid cluster C personality disorder--accounted for more extensive reductions in the ACC and OFC volume. CONCLUSIONS In complex PTSD, not only the hippocampus and the ACC but also the OFC seem to be affected, even in the absence of comorbid borderline personality disorder. These results suggest that neural correlates of complex PTSD are more severe than those of classic PTSD.

Increased activation of the left hippocampus region in Complex PTSD during encoding and recognition of emotional words: a pilot study.

To gain insight into memory disturbances in Complex Posttraumatic Stress Disorder (Complex PTSD), we investigated declarative memory function and medial temporal lobe activity in patients and healthy non-traumatized controls. A case-control study was performed in nine patients with Complex PTSD and nine controls. All respondents performed a declarative memory task with neutral and emotional, negative words during functional magnetic resonance imaging. Memory performance of neutral words was impaired in Complex PTSD with a relative conservation of recall of negative words. Deep encoding of later remembered negative words, as well as correct recognition of negative words and false alarms, was associated with an enhanced Blood Oxygenation Level Dependent (BOLD) response in the left hippocampus extending into the parahippocampal gyrus of Complex PTSD patients compared with controls. Post-hoc volumetric comparisons did not reveal significant anatomical differences in the medial temporal lobe between Complex PTSD patients and controls. We conclude that in Complex PTSD preferential recall of negative words is associated with increased activation in the left hippocampus and parahippocampal gyrus during both successful and false recall. These findings support a model of an abnormally functioning hippocampus in Complex PTSD.

Treatment compliance and effectiveness in complex PTSD patients with co-morbid personality disorder undergoing stabilizing cognitive behavioral group treatment: a preliminary study

Background In the empirical and clinical literature, complex posttraumatic stress disorder (PTSD) and personality disorders (PDs) are suggested to be predictive of drop-out or reduced treatment effectiveness in trauma-focused PTSD treatment. Objective In this study, we aimed to investigate if personality characteristics would predict treatment compliance and effectiveness in stabilizing complex PTSD treatment. Method In a randomized controlled trial on a 20-week stabilizing group cognitive behavioral treatment (CBT) for child-abuse-related complex PTSD, we included 71 patients of whom 38 were randomized to a psycho-educational and cognitive behavioral stabilizing group treatment. We compared the patients with few PD symptoms (adaptive) (N=14) with the non-adaptive patients (N=24) as revealed by a cluster analysis. Results We found that non-adaptive patients compared to the adaptive patients showed very low drop-out rates. Both non-adaptive patients, classified with highly different personality profiles “withdrawn” and “aggressive,” were equally compliant. With regard to symptom reduction, we found no significant differences between subtypes. Post-hoc, patients with a PD showed lower drop-out rates and higher effect sizes in terms of complex PTSD severity, especially on domains that affect regulation and interpersonal problems. Conclusions Contrary to our expectations, these preliminary findings indicate that this treatment is well tolerated by patients with a variety of personality pathology. Larger sample sizes are needed to study effectiveness for subgroups of complex PTSD patients.

Increased anterior cingulate cortex and hippocampus activation in Complex PTSD during encoding of negative words

Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients--compared to controls--encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.

Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder.

BACKGROUND Functional neuroimaging studies have shown increased Stroop interference coupled with altered anterior cingulate cortex (ACC) and insula activation in post-traumatic stress disorder (PTSD). These brain areas are associated with error detection and emotional arousal. There is some evidence that treatment can normalize these activation patterns. METHOD At baseline, we compared classic and emotional Stroop performance and blood oxygenation level-dependent responses (functional magnetic resonance imaging) of 29 child abuse-related complex PTSD patients with 22 non-trauma-exposed healthy controls. In 16 of these patients, we studied treatment effects of psycho-educational and cognitive behavioural stabilizing group treatment (experimental treatment; EXP) added to treatment as usual (TAU) versus TAU only, and correlations with clinical improvement. RESULTS At baseline, complex PTSD patients showed a trend for increased left anterior insula and dorsal ACC activation in the classic Stroop task. Only EXP patients showed decreased dorsal ACC and left anterior insula activation after treatment. In the emotional Stroop contrasts, clinical improvement was associated with decreased dorsal ACC activation and decreased left anterior insula activation. CONCLUSIONS We found further evidence that successful treatment in child abuse-related complex PTSD is associated with functional changes in the ACC and insula, which may be due to improved selective attention and lower emotional arousal, indicating greater cognitive control over PTSD symptoms.

Can pharmacological and psychological treatment change brain structure and function in PTSD? A systematic review

While there is evidence of clinical improvement of posttraumatic stress disorder (PTSD) with treatment, its neural underpinnings are insufficiently clear. Moreover, it is unknown whether similar neurophysiological changes occur in PTSD specifically after child abuse, given its enduring nature and the developmental vulnerability of the brain during childhood. We systematically reviewed PTSD treatment effect studies on structural and functional brain changes from PubMed, EMBASE, PsycINFO, PILOTS and the Cochrane Library. We included studies on adults with (partial) PTSD in Randomized Controlled Trials (RCT) or pre-post designs (excluding case studies) on pharmacotherapy and psychotherapy. Risk of bias was evaluated independently by two raters. Brain coordinates and effect sizes were standardized for comparability. We included 15 studies (6 RCTs, 9 pre-post), four of which were on child abuse. Results showed that pharmacotherapy improved structural abnormalities (i.e., increased hippocampus volume) in both adult-trauma and child abuse related PTSD (3 pre-post studies). Functional changes were found to distinguish between groups. Adult-trauma PTSD patients showed decreased amygdala and increased dorsolateral prefrontal activations post-treatment (4 RCTs, 5 pre-post studies). In one RCT, child abuse patients showed no changes in the amygdala, but decreased dorsolateral prefrontal, dorsal anterior cingulate and insula activation post-treatment. In conclusion, pharmacotherapy may reduce structural abnormalities in PTSD, while psychotherapy may decrease amygdala activity and increase prefrontal, dorsal anterior cingulate and hippocampus activations, that may relate to extinction learning and re-appraisal. There is some evidence for a distinct activation pattern in child abuse patients, which clearly awaits further empirical testing.

Stabilizing Group Treatment for Complex Posttraumatic Stress Disorder Related to Child Abuse Based on Psychoeducation and Cognitive Behavioural Therapy: A Multisite Randomized Controlled Trial

Background: Evidence-based treatments for complex posttraumatic stress disorder (PTSD) related to childhood abuse are scarce. This is the first randomized controlled trial to test the efficacy of psycho-educational and cognitive behavioural stabilizing group treatment in terms of both PTSD and complex PTSD symptom severity. Methods: Seventy-one patients with complex PTSD and severe comorbidity (e.g. 74% axis II comorbidity) were randomly assigned to either a 20-week group treatment in addition to treatment as usual or to treatment as usual only. Primary outcome measures were the Davidson Trauma Scale (DTS) for PTSD and the Structured Interview for Disorders of Extreme Stress (SIDES) for complex PTSD symptoms. Statistical analysis was conducted in the intention-to-treat (ITT) and in the completer sample. Subjects were considered responders when scoring at 20 weeks at least 1 standard deviation below pretest findings. Results: The 16% attrition was relatively low. After 20 weeks, the experimental condition (large effect sizes) and control condition (medium effect sizes) both showed significant decreases on the DTS and SIDES, but differences between the conditions were not significant. The secondary responder analysis (ITT) revealed significantly more responders on the DTS (45 vs. 21%), but not on the SIDES (61 vs. 42%). Conclusions: Adding psycho-educational and cognitive behavioural stabilizing group treatment for complex PTSD related to child abuse to treatment as usual showed an equivocal outcome. Patients in both conditions improved substantially during stabilizing treatment, and while significant superiority on change scores was absent, responder analysis suggested clinical meaningfulness of adding group treatment.

Stabilizing group treatment for Complex Posttraumatic Stress Disorder related to childhood abuse based on psycho-education and cognitive behavioral therapy: A pilot study

OBJECTIVE This study tests a Stabilizing Group Treatment protocol, designed for the management of the long-term sequelae of child abuse, that is, Complex Posttraumatic Stress Disorder (Complex PTSD). Evidence-based treatment for this subgroup of PTSD patients is largely lacking. This stabilizing treatment aims at improving Complex PTSD using psycho-education and cognitive behavioral interventions. METHOD Thirty-six patients with a history of childhood abuse, Complex PTSD and severe co-morbidity entered a 20-week treatment with pre-, post-, and follow-up-assessments. RESULTS Improvement was found for PTSD and borderline symptoms. Post-treatment 64% and after 6 months 78% of patients no longer met criteria for Complex PTSD. CONCLUSIONS This open study indicates both the feasibility of investigating treatment outcome and the initial efficacy of stabilizing group treatment in severely ill patients with Complex PTSD related to childhood abuse.

Evidence-based treatment for adult women with child abuse-related Complex PTSD: a quantitative review

Introduction Effective first-line treatments for posttraumatic stress disorder (PTSD) are well established, but their generalizability to child abuse (CA)-related Complex PTSD is largely unknown. Method A quantitative review of the literature was performed, identifying seven studies, with treatments specifically targeting CA-related PTSD or Complex PTSD, which were meta-analyzed, including variables such as effect size, drop-out, recovery, and improvement rates. Results Only six studies with one or more cognitive behavior therapy (CBT) treatment conditions and one with a present centered therapy condition could be meta-analyzed. Results indicate that CA-related PTSD patients profit with large effect sizes and modest recovery and improvement rates. Treatments which include exposure showed greater effect sizes especially in completers’ analyses, although no differential results were found in recovery and improvement rates. However, results in the subgroup of CA-related Complex PTSD studies were least favorable. Within the Complex PTSD subgroup, no superior effect size was found for exposure, and affect management resulted in more favorable recovery and improvement rates and less drop-out, as compared to exposure, especially in intention-to-treat analyses. Conclusion Limited evidence suggests that predominantly CBT treatments are effective, but do not suffice to achieve satisfactory end states, especially in Complex PTSD populations. Moreover, we propose that future research should focus on direct comparisons between types of treatment for Complex PTSD patients, thereby increasing generalizability of results.

Posttraumatic stress disorder under ongoing threat: a review of neurobiological and neuroendocrine findings

Background Although numerous studies have investigated the neurobiology and neuroendocrinology of posttraumatic stress disorder (PTSD) after single finished trauma, studies on PTSD under ongoing threat are scarce and it is still unclear whether these individuals present similar abnormalities. Objective The purpose of this review is to present the neurobiological and neuroendocrine findings on PTSD under ongoing threat. Ongoing threat considerably affects PTSD severity and treatment response and thus disentangling its neurobiological and neuroendocrine differences from PTSD after finished trauma could provide useful information for treatment. Method Eighteen studies that examined brain functioning and cortisol levels in relation to PTSD in individuals exposed to intimate partner violence, police officers, and fire fighters were included. Results Hippocampal volume was decreased in PTSD under ongoing threat, although not consistently associated with symptom severity. The neuroimaging studies revealed that PTSD under ongoing threat was not characterized by reduced volume of amygdala or parahippocampal gyrus. The neurocircuitry model of PTSD after finished trauma with hyperactivation of amygdala and hypoactivation of prefrontal cortex and hippocampus was also confirmed in PTSD under ongoing threat. The neuroendocrine findings were inconsistent, revealing increased, decreased, or no association between cortisol levels and PTSD under ongoing threat. Conclusions Although PTSD under ongoing threat is characterized by abnormal neurocircuitry patterns similar to those previously found in PTSD after finished trauma, this is less so for other neurobiological and in particular neuroendocrine findings. Direct comparisons between samples with ongoing versus finished trauma are needed in future research to draw more solid conclusions before administering cortisol to patients with PTSD under ongoing threat who may already exhibit increased endogenous cortisol levels. Highlights of the article We reviewed the neurobiological and neuroendocrine findings in PTSD under ongoing threat. PTSD under ongoing threat demonstrated similar brain abnormalities as PTSD after finished trauma. Several studies found increased cortisol levels in PTSD under ongoing threat. Hydrocortisone administration might not be beneficial for individuals with PTSD under ongoing threat with elevated endogenous cortisol levels. Direct comparisons between ongoing versus finished trauma are needed to provide robust conclusions and clinical recommendations.