Posttraumatic Stress Disorder Treatment Response Research Articles

Emotion regulation and heart rate variability may identify the optimal posttraumatic stress disorder treatment: analyses from a randomized controlled trial.

High variability in response and retention rates for posttraumatic stress disorder (PTSD) treatment highlights the need to identify "personalized" or "precision" medicine factors that can inform optimal intervention selection before an individual commences treatment. In secondary analyses from a non-inferiority randomized controlled trial, behavioral and physiological emotion regulation were examined as non-specific predictors (that identify which individuals are more likely to respond to treatment, regardless of treatment type) and treatment moderators (that identify which treatment works best for whom) of PTSD outcome. There were 85 US Veterans with clinically significant PTSD symptoms randomized to 6 weeks of either cognitive processing therapy (CPT; n = 44) or a breathing-based yoga practice (Sudarshan kriya yoga; SKY; n = 41). Baseline self-reported emotion regulation (Difficulties in Emotion Regulation Scale) and heart rate variability (HRV) were assessed prior to treatment, and self-reported PTSD symptoms were assessed at baseline, end-of-treatment, 1-month follow-up, and 1-year follow-up. Greater baseline deficit in self-reported emotional awareness (similar to alexithymia) predicted better overall PTSD improvement in both the short- and long-term, following either CPT or SKY. High self-reported levels of emotional response non-acceptance were associated with better PTSD treatment response with CPT than with SKY. However, all significant HRV indices were stronger moderators than all self-reported emotion regulation scales, both in the short- and long-term. Veterans with lower baseline HRV had better PTSD treatment response with SKY, whereas Veterans with higher or average-to-high baseline HRV had better PTSD treatment response with CPT. To our knowledge, this is the first study to examine both self-reported emotion regulation and HRV, within the same study, as both non-specific predictors and moderators of PTSD treatment outcome. Veterans with poorer autonomic regulation prior to treatment had better PTSD outcome with a yoga-based intervention, whereas those with better autonomic regulation did better with a trauma-focused psychological therapy. Findings show potential for the use of HRV in clinical practice to personalize PTSD treatment. ClinicalTrials.gov identifier, NCT02366403.

Predicting Post-Traumatic Stress Disorder Treatment Response Using Heart Rate Variability to Virtual Reality Environment and Modified Stroop Task: An Exploratory Study.

Predicting treatment response can inform treatment decisions, expectations, and optimize use of mental health treatment resources. This study examined heart rate (HR), heart rate variability (HRV), and a modified Stroop task (mStroop) to predict post-traumatic stress disorder (PTSD) treatment response. We report on an observational, longitudinal study with 45 U.S. veterans in outpatient PTSD care, who had deployed to Iraq or Afghanistan. HR and HRV were collected before, during, and after virtual reality (VR) combat and civilian scenes. HRV recovery was defined as HRV after a 3-minute VR simulation minus HRV during a VR scene. mStroop threat variables included index scores for combat and general threat. Self-report data were collected at baseline and 6 months later. The outcome variable was the 17-item Clinician Administered PTSD Scale (CAPS). Controlling for baseline CAPS and number of combat experiences, the following baseline HRV recovery variables were significant predictors of 6-month CAPS: standard deviation of normal beat to beat interval (SDNN) after combat scene minus SDNN during combat scene and low-frequency (LF HRV) after civilian scene minus LF during civilian scene. HRV at rest, HR reactivity, HR recovery, and mStroop scores did not predict treatment response. In conclusion, HRV recovery variables in the context of a standardized VR stressor were significant predictors of PTSD treatment response after controlling for baseline CAPS and number of combat experiences. The direction of this relationship indicates that greater baseline HRV recovery predicts lower 6-month PTSD symptom severity. This was an exploratory study in need of replication.

Implicit trauma identity associations in treatment-seeking U.S. military personnel do not predict or change in response to cognitive processing therapy for PTSD.

This study evaluated implicit associations (i.e., associations in memory that are automatically activated and difficult to control consciously) related to trauma and one's self in the context of a clinical trial for active duty service members seeking treatment for posttraumatic stress disorder (PTSD). Previous studies with nontreatment-seeking community samples found that implicit trauma identity associations were associated with PTSD symptoms even after controlling for amount of trauma exposure and self-reported negative cognitions about the self. This study extended prior work by evaluating whether trauma-related implicit associations were associated with PTSD and depressive symptoms in a clinical sample seeking treatment for PTSD, predicted PTSD treatment response, or changed over the course of treatment. This secondary analysis examined implicit trauma identity associations using data from a clinical trial evaluating a variable-length adaptation of cognitive processing therapy for military personnel. Participants were 127 active duty U.S. military personnel (13.4% women) seeking PTSD treatment. Implicit trauma identity associations were evaluated at baseline and posttreatment. Study hypotheses and data analysis plan were preregistered. Contrary to predictions, baseline implicit trauma identity associations were not significantly associated with baseline PTSD or depressive symptoms and did not predict treatment response. Implicit trauma identity associations did not change significantly in response to treatment. More tailoring of implicit trauma measures for military personnel and/or treatment-seeking patients may be needed. The measure may lack sensitivity to change in response to treatment and have reduced utility in treatment-seeking samples with high symptom burden and less variability in symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mitochondrial DNA as a marker for treatment-response in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a serious mental health condition thought to be mediated by a dysregulated stress response system. Stress, especially chronic stress, affects mitochondrial activity and their efficiency in duplicating their genomes. Human cells contain numerous mitochondria that harbor multiple copies of their own genome, which consist of a mixture of wild type and variant mtDNA - a condition known as mitochondrial heteroplasmy. Number of mitochondrial genomes in a cell and the degree of heteroplasmy may serve as an indicator of mitochondrial allostatic load. Changes in mtDNA copy number and the proportion of variant mtDNA may be related to mental disorders and symptom severity, suggesting an involvement of mitochondrial dysfunction also in PTSD. Therefore, we examined number and composition of mitochondrial DNA before and after six weeks of inpatient psychotherapy treatment in a cohort of 60 female PTSD patients. We extracted DNA from isolated monocytes before and after inpatient treatment and quantified cellular mtDNA using multiplex qPCR. We hypothesized that treatment would lead to changes in cellular mtDNA levels and that change in mtDNA level would be associated with PTSD symptom severity and treatment response. It could be shown that mtDNA copy number and the ratio of variant mtDNA decreased during therapy, however, this change did not correlate with treatment response. Our results suggest that inpatient treatment can reduce signs of mitochondrial allostatic load, which could have beneficial effects on mental health. The quantification of mtDNA and the determination of cellular heteroplasmy could represent valuable biomarkers for the molecular characterization of mental disorders in the future.

Moving toward precision PTSD treatment: predicting veterans' intensive PTSD treatment response using continuously updating machine learning models.

Considerable heterogeneity exists in treatment response to first-line posttraumatic stress disorder (PTSD) treatments, such as Cognitive Processing Therapy (CPT). Relatively little is known about the timing of when during a course of care the treatment response becomes apparent. Novel machine learning methods, especially continuously updating prediction models, have the potential to address these gaps in our understanding of response and optimize PTSD treatment. Using data from a 3-week (n = 362) CPT-based intensive PTSD treatment program (ITP), we explored three methods for generating continuously updating prediction models to predict endpoint PTSD severity. These included Mixed Effects Bayesian Additive Regression Trees (MixedBART), Mixed Effects Random Forest (MERF) machine learning models, and Linear Mixed Effects models (LMM). Models used baseline and self-reported PTSD symptom severity data collected every other day during treatment. We then validated our findings by examining model performances in a separate, equally established, 2-week CPT-based ITP (n = 108). Results across approaches were very similar and indicated modest prediction accuracy at baseline (R2 ~ 0.18), with increasing accuracy of predictions of final PTSD severity across program timepoints (e.g. mid-program R2 ~ 0.62). Similar findings were obtained when the models were applied to the 2-week ITP. Neither the MERF nor the MixedBART machine learning approach outperformed LMM prediction, though benefits of each may differ based on the application. Utilizing continuously updating models in PTSD treatments may be beneficial for clinicians in determining whether an individual is responding, and when this determination can be made.

Spontaneous brain activity, graph metrics, and head motion related to prospective post-traumatic stress disorder trauma-focused therapy response.

IntroductionTrauma-focused psychotherapy for post-traumatic stress disorder (PTSD) is effective in about half of all patients. Investigating biological systems related to prospective treatment response is important to gain insight in mechanisms predisposing patients for successful intervention. We studied if spontaneous brain activity, brain network characteristics and head motion during the resting state are associated with future treatment success.MethodsFunctional magnetic resonance imaging scans were acquired from 46 veterans with PTSD around the start of treatment. Psychotherapy consisted of trauma-focused cognitive behavioral therapy (tf-CBT), eye movement desensitization and reprocessing (EMDR), or a combination thereof. After intervention, 24 patients were classified as treatment responders and 22 as treatment resistant. Differences between groups in spontaneous brain activity were evaluated using amplitude of low-frequency fluctuations (ALFF), while global and regional brain network characteristics were assessed using a minimum spanning tree (MST) approach. In addition, in-scanner head motion was assessed.ResultsNo differences in spontaneous brain activity and global network characteristics were observed between the responder and non-responder group. The right inferior parietal lobule, right putamen and left superior parietal lobule had a more central position in the network in the responder group compared to the non-responder group, while the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal gyrus and left inferior temporal gyrus had a less central position. In addition, responders showed less head motion.DiscussionThese results show that areas involved in executive functioning, attentional and action processes, learning, and visual-object processing, are related to prospective PTSD treatment response in veterans. In addition, these findings suggest that involuntary micromovements may be related to future treatment success.

A clinical trial comparing trauma-informed guilt reduction therapy (TrIGR), a brief intervention for trauma-related guilt, to supportive care therapy.

Trauma-related guilt is common, associated with posttraumatic mental health problems, and can persist after posttraumatic stress disorder (PTSD) treatment. We compared the efficacy of two six-session psychotherapies, Trauma-Informed Guilt Reduction (TrIGR) and Supportive Care Therapy (SCT), for reducing trauma-related guilt. TrIGR helps patients accurately appraise their role in the trauma and re-engage in values. In SCT, patients guide session content. A total of 184 veterans seeking VA mental health services were enrolled across two sites; 145 veterans (mean age: 39.2 [8.1]; 92.4% male; 84.8% with PTSD) who endorsed guilt related to a traumatic event that occurred during a post 9/11 Iraq or Afghanistan deployment were randomized and assessed at baseline, posttreatment, 3- and 6-month follow-up. Linear mixed models using intent-to-treat analyses showed guilt decreased in both conditions with a greater decrease for TrIGR (treatment × time, -0.22; F 1, 455.2 = 18.49, p = .001; d = 0.92) than supportive therapy. PTSD and depressive symptoms showed the same pattern. TrIGR had significantly higher likelihood of PTSD treatment response (67% vs. 40%), loss of PTSD diagnosis (50% vs. 14%), and meaningful change in depression (54% vs. 27%) than supportive therapy. Psychological distress and trait shame improved in both conditions. Quality of life did not change. Targeting guilt appears to be an effective means for reducing posttraumatic symptoms and distress.

Intensive Outpatient Program Using Prolonged Exposure for Combat-Related PTSD: A Case Study

Although prolonged exposure (PE) has been identified as a first-line treatment for posttraumatic stress disorder (PTSD), research has found that military service members and veterans have smaller reductions in symptom severity compared to civilians. The nature of trauma in a deployed combat setting and the unique complexities of military culture have been proposed as explanations for greater rates of PTSD and poorer treatment response to first-line psychotherapies in military and veteran populations. This paper presents a case study to highlight how a novel, intensive outpatient program utilizing prolonged exposure therapy (IOP-PE) may benefit military personnel with combat-related PTSD. The patient is a Caucasian man in his early 40s seeking treatment for PTSD after more than 10 years of enlisted, active duty military service across two branches and three combat deployments. The IOP-PE includes the standard PE components and eight, nonstandard treatment augmentations tailored for military personnel. In contrast to standard PE, which typically is delivered weekly over several months, IOP-PE consists of 15 daily, 90-minute PE sessions conducted over 3 weeks. The patient demonstrated large reductions on the Clinician-Administered PTSD Scale (28 points) and PTSD Checklist (48 points) by the 6-month posttreatment follow-up point. Findings provide support for conducting further research that determines whether IOP-PE is effective and tolerable in military and veteran populations.

Investigating the link between subjective sleep quality, symptoms of PTSD, and level of functioning in a sample of trauma-affected refugees.

To examine whether baseline sleep quality is associated with baseline symptoms of posttraumatic stress disorder (PTSD) and level of functioning and whether baseline sleep quality and improvement of sleep quality are specific predictors of change in PTSD symptoms and level of functioning. Data were derived from a four-armed randomized controlled superiority trial (N = 219 trauma-affected refugees). All four groups received treatment as usual consisting of a 10-12 months bio-psycho-social treatment program with an additional differential treatment component added to each arm. We performed bivariate correlation analyses, multiple linear regression analyses, and mediation analyses to examine associations between baseline sleep quality, change in sleep quality, and treatment response for PTSD symptoms and level of functioning. Baseline sleep quality correlated with symptoms of PTSD (r = 0.33) and level of functioning (r = 0.15). Baseline sleep quality, improvement of sleep quality, and improvement of general well-being were predictors of treatment response for symptoms of PTSD and level of functioning when controlling for age, gender, and baseline symptoms of PTSD and depression. We found that good sleep quality at baseline and improvement of sleep quality were predictors of PTSD treatment response. However, treatment response was more closely associated with improvement in general well-being. The results indicate that the effect of improved sleep quality was partly mediated by a more general mental state improvement. Further research is needed to differentiate if a selected subgroup of patients may profit from sleep-enhancing treatment. NCT02761161.

Latent Profiles of Comorbid Depression as Predictors of PTSD Treatment Outcome

Posttraumatic stress disorder (PTSD) frequently co-occurs with major depressive disorder, and empirically supported PTSD treatments consistently improve depression. However, both diagnoses are heterogeneous and specific patterns of symptom overlap may be related to worse treatment outcome. Two hundred individuals with chronic PTSD participated in a doubly randomized preference trial comparing prolonged exposure and sertraline. Latent Profile Analysis was used to identify classes based on PTSD and depression symptoms prior to starting treatment. A three-class model best fit the data, with a high depression and PTSD severity class (distressed), a moderate depression and low PTSD avoidance class (depressive), and a low depression and high PTSD avoidance class (avoidant). The avoidant class showed the lowest rates of major depressive disorder diagnosis and transdiagnostic vulnerabilities to depression. Patients in the distressed class experienced more robust PTSD treatment response, with no differences between prolonged exposure and sertraline. These findings highlight the role of avoidance in nondepressed PTSD presentations while also demonstrating that co-occurring depression is not contraindicated in evidence-based PTSD treatment.

Defining response and nonresponse to posttraumatic stress disorder treatments: A systematic review.

There is currently no uniform definition of treatment response for posttraumatic stress disorder (PTSD) to guide researchers and clinicians in the area of posttraumatic mental health. The aim of this systematic review was to explore the operationalization of PTSD treatment response, by reviewing and synthesizing the key criteria used to define treatment response and treatment nonresponse in published trials. Randomized controlled trials (RCTs) assessing the effectiveness of first-line interventions for PTSD were identified for inclusion. Of those, 143 trials provided 226 definitions of treatment response, grouped under five main categories: treatment response (n = 181), remission (n = 23), recovery (n = 5), treatment nonresponse (n = 5), and worsening (n = 12). Overall, the results showed the PTSD field utilizes diverse and interchangeable operational definitions of treatment response and nonresponse, indicating a need for more precise conceptual definitions and operational criteria. A set of operational research definitions are presented in order to advance the PTSD treatment field.

Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder.

Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN). At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042). Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

A Preliminary Examination of Endogenous Peripheral Oxytocin in a Pilot Randomized Clinical Trial of Oxytocin-Enhanced Psychotherapy for Posttraumatic Stress Disorder.

Preclinical and clinical research suggests that the oxytocin system is implicated in the development and maintenance of stress and anxiety-related psychiatric conditions, such as posttraumatic stress disorder (PTSD). Recent research also suggests that intranasal oxytocin holds promise as a treatment for PTSD. However, little is known about the relationship between levels of peripheral oxytocin and PTSD symptom severity, PTSD treatment response, and repeated intranasal oxytocin administration. In the current study, we examined associations between PTSD symptom severity and peripheral oxytocin levels measured in plasma before and after a course of prolonged exposure (PE) for PTSD (n = 13); participants were randomized to adjunctive intranasal oxytocin (n = 6) or placebo (n = 7). Baseline peripheral oxytocin levels were not associated with baseline PTSD symptom severity. Change in peripheral oxytocin levels did not differ by treatment condition and did not correspond to change in PTSD symptoms. This proof-of-concept study illustrates the acceptability and feasibility of measuring peripheral oxytocin among individuals engaged in psychotherapy for PTSD and informs the utilization of these procedures in future adequately powered studies.

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial

Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. Prolonged Exposure (PE) therapy is one of the most widely used evidence-based treatments for PTSD, but there is substantial room for improvement in outcomes and retention rates. Accumulating data suggest that oxytocin offers a promising pharmacological approach towards achieving this goal. Therefore, the primary objective of this two-site Phase II study is to examine the ability of oxytocin (vs. placebo) administration combined with PE therapy to (1) reduce PTSD symptom severity, (2) accelerate the rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). Intranasal oxytocin (40 IU) will be administered directly prior to each PE therapy session. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the physiological mechanisms underlying PTSD and positive treatment response. ClinicalTrials.gov Identifier: NCT04228289

Neuroendocrine biomarkers of prolonged exposure treatment response in military-related PTSD

Posttraumatic stress disorder (PTSD) is associated with dysregulation of the neuroendocrine system, including cortisol, allopregnanolone, and pregnanolone. Preliminary evidence from animal models suggests that baseline levels of these biomarkers may predict response to PTSD treatment. We report the change in biomarkers over the course of PTSD treatment. Biomarkers were sampled from individuals participating in (1) a randomized controlled trial comparing a web-version of Prolonged Exposure (Web-PE) therapy to in-person Present-Centered Therapy (PCT) and (2) from individuals participating in a nonrandomized effectiveness study testing PE delivered in-person as part of an intensive outpatient PTSD program. We found that higher cortisol reactivity during script-driven imagery was associated with higher baseline PTSD severity and that baseline allopregnanolone, pregnanolone, and cortisol reactivity were associated with degree of symptom change over the course of intensive outpatient treatment. These findings demonstrate that peripherally assessed biomarkers are associated with PTSD severity and likelihood of successful treatment outcome of PE delivered daily over two weeks. These assessments could be used to determine which patients are likely to respond to treatment and which patients require augmentation to increase the likelihood of optimal response to PTSD treatment.

PTSD treatment response and quality of life in women with childhood trauma histories.

Childhood trauma is associated with greater psychological problems and poorer quality of life (QOL). This study evaluates the effect of multiple types of childhood trauma on posttraumatic stress disorder (PTSD) and QOL following cognitive processing therapy (CPT). Understanding how the breadth of traumatic experiences in childhood can influence psychosocial treatment outcomes may help to identify the unique needs of this population. This secondary data analysis of a randomized controlled trial delivering CPT to civilian (n = 105) and veteran women (n = 21) with PTSD used linear regressions to examine relationships between the number of unique types of childhood trauma, PTSD, and QOL before and after treatment. Models controlled for demographic information, adult trauma, and pretreatment PTSD, depression, and QOL scores. More types of childhood trauma predicted pretreatment PTSD symptoms (B = 1.98, p = .02) but not QOL (B = -.018, p = .18). Significant reductions in Clinician-Administered PTSD Scale for DSM-IV-TR score, t(302) = 10.32, p < .001, and QOL, t(309) = -4.06, p < .001, were reported after treatment; number of traumatic event types was not predictive of QOL change (B = .01, p = .957). Women with more types of trauma reported significantly less PTSD symptom reduction when compared with those with one type (B = 3.12, p = .042). Women who experienced a broader range of childhood trauma may experience diminished PTSD symptom reduction following CPT in comparison with women with less exposure. On average, all women, regardless of trauma history, reported small improvements in QOL. Clinical considerations are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Understanding the impact of complicated grief on combat related posttraumatic stress disorder, guilt, suicide, and functional impairment in a clinical trial of post-9/11 service members and veterans.

Complicated grief (CG) is a bereavement-specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes. To evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat-related PTSD (n = 194). Assessment of PTSD, trauma-related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24-week trial. CG was associated with lower PTSD treatment response (odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.12, 0.69], p = 0.005) and remission (OR = 0.28, 95% CI [0.11, 0.71], p = 0.007). Those with CG had greater severity of PTSD (p = 0.005) and trauma-related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR = 3.01, 95% CI [1.29, 7.02], p = 0.011). Comorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat-related PTSD, suggesting that screening and additional intervention for CG may be needed.

Sexual Desire among Veterans Receiving Prolonged Exposure Therapy for PTSD: Does Successful PTSD Treatment Also Yield Improvements in Sexual Desire?

Objective: People with posttraumatic stress disorder (PTSD) commonly report difficulties with sexual desire and other aspects of sexual functioning, but it is currently unknown if people who respond to psychotherapy for PTSD also report improvements in sexual desire. Method: One hundred and eighty-seven veterans with PTSD received prolonged exposure (PE) therapy at two outpatient PTSD specialty clinics and completed measures of PTSD symptoms (the PTSD Checklist – Military Version) and sexual desire (item 21 of the Beck Depression Inventory – Second Edition) repeatedly throughout the course of treatment. Results: The results of a conditional generalized mixed ordinal regression model showed a significant interaction between weeks in treatment and PTSD treatment response in predicting change in sexual desire across the course of treatment. Specifically, PTSD treatment responders reported improvement in sexual desire over the course of treatment, whereas nonresponders did not show changes in sexual desire over time. However, the effect of PTSD treatment response was no longer significant when accounting for severity of depression at the start of treatment. Participants reporting more severe depression at the start of treatment reported less improvement in sexual desire, regardless of PTSD symptom response. Conclusions: People with PTSD who respond to PE also report improvements in sexual desire over time, indicating that response to PE is associated with improved sexual desire, but the effect is complicated by the presence of co-occurring depression symptomatology.

Chapter 20 - Cingulate subregions in posttraumatic stress disorder, chronic stress, and treatment

Decades of research have revealed that the cingulate cortex is important in posttraumatic stress disorder (PTSD). Initially inspired by basic rodent research examining the mechanisms of fear learning, researchers have attempted to determine the respective roles of the anterior cingulate cortex (ACC), anterior midcingulate cortex (aMCC), and posterior cingulate cortex (PCC) in PTSD. Various neuroimaging techniques have shown the ACC is both functionally hypoactive and structurally diminished in PTSD, while the aMCC is functionally hyperactive and structurally diminished. Relatedly, chronic stress has been shown to be a significant vulnerability factor in the development of PTSD after a traumatic event, inspiring research into the effect of chronic stress on brain activation and structure. Similar to patterns in PTSD, perceived work-related stress, outgroup membership, and lower socioeconomic status appear to negatively affect cingulate function and morphology. While great strides have been made to understand better the ACC, aMCC, and PCC in both PTSD and chronic stress, additional studies are needed to determine the origin of these cingulate abnormalities and whether they can be used as biomarkers in assessing and predicting treatment response in PTSD.

Effects of intranasal oxytocin on distraction as emotion regulation strategy in patients with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is characterized by difficulty down-regulating emotional responses towards trauma-reminders. The neuropeptide oxytocin may enhance treatment response in PTSD, by dampening excessive fear and improving fear regulation. However, oxytocin effects on (neural correlates of) cognitive emotion regulation abilities have never been investigated in PTSD patients. Therefore, we investigated behavioral and neural effects of intranasal oxytocin administration (40IU) on distraction as emotion regulation strategy in male and female police officers with and without PTSD (n = 76), using a randomized placebo-controlled cross-over fMRI study. The distraction condition consisted of a working memory task while negative affective pictures were presented. Under placebo, male PTSD patients showed decreased right striatal activity during distraction compared to male trauma-exposed controls, which was unaffected by oxytocin. After oxytocin administration, left thalamus activity during distraction was enhanced in all participants, independent of PTSD status or sex. Although left thalamus activity during distraction did not differ between PTSD patients and controls under placebo, it was negatively correlated with error rates within PTSD patients. Furthermore, oxytocin administration increased functional connectivity between the left thalamus and amygdala in PTSD patients and male trauma-exposed controls. Upregulation of thalamus activity during distraction by oxytocin may enhance cognitive emotion regulation abilities during psychotherapy in PTSD, although this should still be investigated in a clinical setting. Our findings open an important research avenue into oxytocin effects on cognitive emotion regulation in PTSD and other psychiatric disorders characterized by deficient emotion regulation abilities. Registered in the Netherlands Trial Registry, registration number: NTR3516