Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving ...the detection of salient stimuli (i.e., the salience network SN) and stimulus-independent, internally focused thought (i.e., the default mode network DMN).
Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain.
Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected).
During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.
Background Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have ...shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. Limitations Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD. Conclusion These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.
Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction ...recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.
Although most posttraumatic stress disorder (PTSD) care in the Veterans health administration (VHA) is provided on an outpatient basis, the VHA has 40 residential rehabilitation treatment programs ...(RRTPs) designed to treat Veterans who require more intensive and closely monitored care. Unfortunately, the clinical outcomes of these programs are modest, and previous attempts to identify key drivers of outcomes have uncovered few modifiable factors. The present study, informed by the model of resources, life events and changes in psychological state, was designed to identify factors associated with treatment response among RRTP patients and providers. Semistructured interviews were conducted with 24 patients and 12 providers at three regional RRTPs, using interview guides based on the theoretical model. Data were analyzed using rapid analysis. Results showed that patients and providers agreed on several factors critical to RRTP success. These factors included the provision of evidence-based psychotherapy (EBP), support and understanding from fellow patients, and skill and support from providers. Patients and providers also noted the importance of psychological flexibility, openness, and willingness to change. Patients who experienced less symptom improvement over the course of treatment were more likely to report poor therapeutic alliance. These findings underscore the importance of continued emphasis on EBP delivery but also suggest that RRTPs might find additional ways to capitalize on the residential milieu to encourage engagement in treatment and a focus on therapeutic change.
Impact Statement
When queried about factors that contribute to treatment response in veterans affairs (VA) residential rehabilitation treatment programs for posttraumatic stress disorder, patients and providers agreed that first-line evidence-based treatments, social support from Veterans and providers, and patient openness and willingness to change were all critical components to success. Policy makers and program administrators could consider ways to enhance these elements in residential programs.
Convergent research suggests that childhood poverty is associated with perturbation in the stress response system. This might extend to aberrations in the connectivity of large-scale brain networks, ...which subserve key cognitive and emotional functions. Resting-state brain activity was measured in adults with a documented history of childhood poverty (n=26) and matched controls from middle-income families (n=26). Participants also underwent a standard laboratory social stress test and provided saliva samples for cortisol assay. Childhood poverty was associated with reduced default mode network (DMN) connectivity. This, in turn, was associated with higher cortisol levels in anticipation of social stress. These results suggest a possible brain basis for exaggerated stress sensitivity in low-income individuals. Alterations in DMN may be associated with less efficient cognitive processing or greater risk for development of stress-related psychopathology among individuals who experienced the adversity of chronic childhood poverty.
BACKGROUNDAlthough most veterans with posttraumatic stress disorder (PTSD) benefit from evidence-based treatments, questions persist concerning the profiles of those at risk for poor outcomes. To ...help address these gaps, this study analyzed a large clinical cohort of veterans receiving prolonged exposure (PE) or cognitive processing therapy (CPT). METHODSCluster analysis using Ward's method with Euclidian distances identified clinically meaningful subgroups of veterans in a national cohort (n = 20,848) using variables maintained in the electronic medical record. The clusters were then compared via one-way analysis of variance and Tukey's HSD on indicators of treatment progress including PTSD symptom change, clinical recovery, clinically significant change, remission, and treatment completion. RESULTSEffect size differences on clinical outcome measures for PE and CPT were negligible. Less than half of veterans achieved at least a 15-point reduction in PCL-5 score and half completed treatment. We identified 10 distinct clusters. Higher rates of PTSD service-connected disability were linked to poorer outcomes across multiple clusters, especially when combined with Post-Vietnam service era. Non-White race was also linked with poorer clinical outcomes. Factors associated with better outcomes included a greater proportion of female veterans, especially when combined with recent service era, and longer PTSD diagnosis duration. CONCLUSIONSThis study suggests the need to improve PTSD treatment outcomes for non-White and male veterans, examine treatment response in Post-Vietnam era veterans, and consider ways in which the service connection process could hinder treatment response. The results from this study also indicate the benefits of integrating elements of clinical complexity into an analytic approach.
The U.S. Department of Veterans Affairs (VA) has placed increased emphasis on the availability and use of evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD). However, many ...individuals do not complete a full course of EBP. The current study aimed to quantify the percentage of veterans receiving adequate EBP in VA hospitals and identify factors related to treatment completion.
A national sample of 16,559 VA patients who began cognitive processing therapy (CPT) or prolonged exposure (PE) during fiscal year 2015 was obtained via administrative data. Generalized estimating equations were used to evaluate individual-level predictors of treatment adequacy, defined as eight sessions within 14 weeks. Generalized linear models were used to examine facility-level factors.
A total of 5,142 (31.1%) veterans completed eight or more sessions of psychotherapy. Older age was associated with greater odds of completing eight or more sessions (odds ratio OR=1.02, 95% confidence interval CI=1.01, 1.02, p<0.001), and comorbid bipolar or psychotic disorders were associated with reduced odds of completion (OR=0.89, 95% CI=0.80, 0.99, p=0.03). The percentage of patients who completed eight or more sessions was higher at facilities with higher percentages of EBP use among all patients with PTSD (β=6.55, SE=1.97, p=0.001) and greater numbers of EBP-certified providers (β=0.004, SE=0.002, p=0.038) and lower at facilities with a higher percentage of patients receiving a PTSD Checklist (β=-1.16, SE=0.46, p=0.011).
A minority of VA patients with PTSD complete an adequate dose of EBPs for PTSD. Individual and facility-level factors related to treatment adequacy may point to opportunities for intervention.
Evidence-based treatments for posttraumatic stress disorder (PTSD) often produce significant symptom reduction within eight sessions. However, some patients take longer to respond and a better ...understanding of predictors of later response can help guide treatment. In the current study, the cohort consisted of all VA patients with a PTSD diagnosis who received at least eight sessions of documented evidence-based treatment within a 6-month period in FY16-FY17 and had at least two PTSD symptom assessments. We examined the proportion of patients who achieved meaningful change (defined as at least 50% reduction in self-reported PTSD symptoms), both within the first eight sessions and subsequently. Fourteen percent of patients achieved meaningful change within eight sessions and 10% subsequently. Symptom change within the first eight sessions was highly predictive of subsequent change. Those who experienced at least 20% symptom reduction by session eight were twice as likely to subsequently achieve meaningful change as compared with all patients who continued treatment. Patients receiving service-connected disability compensation were less likely and White patients more likely to achieve meaningful change. Without some degree of symptom reduction by session eight, patients are unlikely to achieve meaningful change if treatment is not enhanced or changed.
•We investigated prevalence and predictors of meaningful PTSD change in VA care•14% of veterans achieved meaningful change within 8 sessions and 10% subsequently•Those without some symptom reduction by session 8 are at high risk for nonresponse
Convergent evidence suggests that individuals with posttraumatic stress disorder (PTSD) exhibit exaggerated avoidance behaviors as well as abnormalities in Pavlonian fear conditioning. However, the ...link between the two features of this disorder is not well understood. In order to probe the brain basis of aberrant extinction learning in PTSD, we administered a multimodal classical fear conditioning/extinction paradigm that incorporated affectively relevant information from two sensory channels (visual and tactile) while participants underwent fMRI scanning. The sample consisted of fifteen OEF/OIF veterans with PTSD. In response to conditioned cues and contextual information, greater avoidance symptomatology was associated with greater activation in amygdala, hippocampus, vmPFC, dmPFC, and insula, during both fear acquisition and fear extinction. Heightened responses to previously conditioned stimuli in individuals with more severe PTSD could indicate a deficiency in safety learning, consistent with PTSD symptomatology. The close link between avoidance symptoms and fear circuit activation suggests that this symptom cluster may be a key component of fear extinction deficits in PTSD and/or may be particularly amenable to change through extinction-based therapies.
Although improving residential PTSD care is a priority for the Department of Veterans Affairs, previous evaluations have been limited by a lack of systematic data collection across more than two ...timepoints. This study used recently available data to assess symptom trajectories in a large, national sample of veterans who engaged in residential PTSD treatment. Group-based trajectory analysis PROC TRAJ was used to identify PTSD residential treatment response in a national cohort of veterans (n = 10,832) and the subset of veterans (n = 6515) receiving evidence-based psychotherapy (EBP). PTSD symptoms were assessed at intake, discharge, and 4-month follow-up. Predictors of trajectory membership were estimated using multinomial models. For the full cohort, a three-group trajectory model provided the best fit with the following identified groups: “Severe/Stable” (51.8%), “Moderate/Rebound” (40.1%), and “Mild/Rebound” (8.1%). For the EBP sub-cohort, a three-group trajectory model was selected with the following groups: “Severe/Stable” (58.5%), “Moderate/Rebound” (34.1%), and “Mild/Rebound” (7.4%). Across all trajectories, psychological distress, pain severity, substance use, Iraq/Afghanistan combat era, non-White race, and treatment dropout were associated with poorer treatment response. In the EBP sub-cohort, homelessness and unemployment at the time of admission were also associated with poorer treatment outcomes to varying degrees. This study demonstrates that residential treatment for PTSD is associated with heterogeneous treatment trajectories which highlight the need to continue to explore and improve residential PTSD treatment outcomes. Our results underscore the importance of obtaining follow-up data and identifying ways to maintain therapeutic gains following discharge.
•We estimated treatment trajectories for a full and EBP subcohort of Veterans.•The full and EBP subcohort demonstrated similar trajectories over three timepoints.•More work is needed to improve maintenance of gains after treatment.
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