non-PTSD Patients Research Articles

Post-Traumatic Stress Disorder as a Risk Factor for Adverse Outcomes in Total Knee Arthroplasty

BackgroundThere is a scarcity of literature concerning individuals who have existing post-traumatic stress disorder (PTSD) and their outcomes after primary total knee arthroplasty (TKA). This study compared outcomes in patients undergoing primary TKA who have a previous history of PTSD. MethodsAn electronic healthcare database was utilized to identify patients diagnosed with PTSD undergoing TKA. Through 1:1 ratio propensity matching, these patients were matched with a cohort of non-PTSD (NPTSD) individuals. Postoperative parameters, including healthcare visits and prescriptions, were assessed within a 1-month timeframe following surgery. Complication and revision rates were evaluated after one month, six months, one year, two years, and five years. A total of 646,186 patients undergoing primary TKA were identified. Ultimately, 7,381 patients who had PTSD were propensity-matched to 7,381 NPTSD patients. ResultsPatients who had PTSD presented to the emergency department (ED) at a higher rate than NPTSD patients within seven days (OR [odds ratio]: 1.5; CI [confidence interval]: 1.0 to 2.4) postoperative. Within one month, cohorts were prescribed opioid analgesics at similar rates (OR: 0.9; CI: 0.8 to 1.1). Patients who had PTSD were found to have a higher number of infections within one month (OR: 1.7 CI: 1.2 to 2.6) and five years (OR: 1.2; CI: 1.0 to 1.5), periprosthetic fractures at six months (OR: 2.1; CI: 1.0 to 4.5) and one year (OR: 2.1; CI: 1. to 4.0), and higher revision rates at all time points. ConclusionPatients diagnosed with PTSD exhibited higher rates of periprosthetic infections at one month and five years and increased periprosthetic fracture rates at six months and one year after TKA compared to NPTSD patients. These findings underscore the importance of tailored early postoperative education and understanding outcomes for patients who have PTSD in contrast to those who do not have a diagnosis of PTSD.

The occurrence of ST elevation myocardial infarction (STEMI) and non-STEMI in patients with post traumatic stress disorder (PTSD) using the large nationwide inpatient sample (NIS).

PTSD leads to increased levels of stress hormones and dysregulation of the autonomic nervous system which may trigger cardiac events. The goal of this study is to evaluate any association between PTSD and the occurrence of STEMI and NSTEMI using a large database. Using the Nationwide Inpatient Sample (NIS) and ICD-9 codes from 2005 to 2014 (n=1,621,382), we performed a univariate chi-square analysis of in-hospital occurrence of STEMI and NSTEMI in patients greater than 40 years of age with and without PTSD. We also performed a multivariate analysis adjusting for baseline characteristics including age, gender, diabetes, race, hyperlipidemia, hypertension, and tobacco use. The 2005-2014 dataset contained 401,485 STEMI patients (745, or 0.19%, with PTSD) and 1,219,897 NSTEMI patients (2,441, or 0.15%, with PTSD). In the 2005 dataset, 0.5% of PTSD patients had STEMI compared to 1.0% of non-PTSD patients (OR=0.46, 95% C.I., 0.36-0.59). Similarly, 0.6% of patients with PTSD and 2.2% of patients without PTSD had NSTEMI (OR=0.28, 95% C.I., 0.23-0.35). In the 2014 dataset, 0.3% of PTSD patients had STEMI compared to 0.7% of non-PTSD patients (OR=0.43, 95% C.I., 0.35-0.51). Similarly, 1.4% of patients with PTSD versus 2.9% of patients without PTSD had NSTEMI (OR=0.48, 95% C.I., 0.44-0.52). Similar trends were seen throughout the ten-year period. After adjusting for age, gender, diabetes, race, hyperlipidemia, hypertension, and tobacco use, PTSD was associated with a lower occurrence of STEMI (2005: OR=0.50, 95% C.I., 0.37-0.66; 2014: OR=0.35, 95% C.I., 0.29-0.43) and NSTEMI (2005: OR=0.44, 95% C.I., 0.34-0.57; 2014: OR=0.63, 95% C.I., 0.58-0.69). Using a large inpatient database, we did not find an increased occurrence of STEMI or NSTEMI in patients diagnosed with PTSD, suggesting that PTSD is not an independent risk factor for myocardial infarction.

Medical cannabis use among patients with Post-Traumatic Stress Disorder (PTSD): A nationwide database study

IntroductionIn recent years, cannabis use among PTSD patients has become more common than ever. However, data available today regarding the effectiveness and safety of medical cannabis in PTSD treatment is limited, based on cross sectional studies, self-report surveys and a few clinical studies with small sample size.ObjectivesTo characterize patterns of use and adverse effects over time in patients with PTSD using medical cannabis in real life setting.MethodsData were acquired from the Israeli national database of all patients licensed to use medical cannabis from January 2014 to December 2021. A license for medical cannabis is given to patients with PTSD of at least moderate intensity after treatment failure of at least two drugs and two psychological interventions. Comparative statistics were used to evaluate patterns of use and adverse effects.Results12,977 patients were licensed to use medical cannabis in the study period for PTSD (8.2% of all users; 70% men) during the above-mentioned time period. PTSD was the 3rd most common indication after chronic pain and symptoms related to oncological disease and chemotherapy treatment. Over time, the relative increase in use of medical cannabis among PTSD patients was higher than that found in non-PTSD patients. In 2021 36.2% of all PTSD patients using medical cannabis had their license issued that year compared to 28.1% of all non-PTSD patients. PTSD patients were significantly younger compared to non-PTSD patients (40.9 years vs. 52.9 years). PTSD patients consume slightly higher monthly amount at the beginning of treatment compared to non-PTSD patients (32.1gr vs. 30.6gr) with higher Tetrahydrocannabinol (THC) concentration (15.2% vs. 12.9%) and lower Cannabidiol (CBD) concentration (4.7% vs. 6.0%). Over two years of use, amount, and composition of cannabis among the two groups were comparable and showed an increase in total amount and THC concentration, reaching the maximal available THC concentration of 20%. Data regarding adverse effects were available for 6,242 PTSD patients (48.1%) and 39,497 non-PTSD patients (26.6%). PTSD patients reported more physical adverse effects (RR 1.45 [95%CI 1.34-1.56]), anxiety (RR 1.47 [95%CI 1.13-1.92]), and derealization (RR 3.44 [95%CI 2.42-4.89]).ConclusionsPTSD is one of the leading indications for medical cannabis use in Israel, despite scarcity in good quality data supporting its effectiveness and safety. The increased risk of mental adverse effects among PTSD patients emphasizes the need for cautious use in cannabis in this population. Expanding the knowledge regarding patterns of use and risks in medical cannabis use among PTSD patients is important for understanding the role of cannabis in PTSD treatment and to ensure an effective and safe treatment.Disclosure of InterestNone Declared

Oral and Dental Considerations of Combat-Induced Post Traumatic Stress Disorder (PTSD)-A Cross-Sectional Study.

Objective: This study compared dental, periodontal, oral, and joint/muscle tenderness among Israeli combat-induced post-traumatic stress disorder (Ci-PTSD) war veterans to non-PTSD patients. Study design: This retrospective three-arm study compared oral and facial manifestations between 100 Israeli veterans with Ci- PTSD (study group) and 103 non-PTSD periodontal patients (Control group). The study group was further divided into two subgroups of individuals who received psychiatric medications (40 patients) or did not (60 patients). All patients underwent complete dental, oral, and periodontal examinations, including assessing signs of parafunction. Results: All PTSD patients had poor oral hygiene. The plaque index (PI) was higher in the PTSD group compared to the control group (0.72 ± 0.28 vs. 0.45 ± 0.29, respectively, p < 0.001). The decayed, missing, and filled teeth score (DMFt) was higher in the PTSD population than in the controls (19.97 ± 8.07 vs. 13.05 ± 6.23 p < 0.05). Severe periodontal disease was more common among the PTSD subgroup taking medications (med -group) (62.5%) compared to the nonmedicated group (non-med group) (30.0%) and the controls (27.2%) (p = 0.001). Heavy smoking was more prevalent in the medicated PTSD patients than in other groups. Conclusions: The present study shows higher morbidities in combat-induced PTSD patients, including oral, dental, and periodontal manifestations, especially in medicated patients.

Acquisition, extinction, and return of fear in veterans in intensive outpatient prolonged exposure therapy: A fear-potentiated startle study

Prolonged exposure (PE) therapy is a first-line treatment for posttraumatic stress disorder (PTSD) and involves repeated presentation of trauma-related cues without aversive outcomes. A primary learning mechanism of PE is fear extinction (new learning that a dangerous cue is now safe) and its retention (maintaining this new learning over time). Extant research suggests extinction is impaired in PTSD patients. In this study, we employed an established fear-potentiated startle-based paradigm to examine fear acquisition, extinction learning and retention before and after completion of intensive outpatient treatment. First, PTSD patients undergoing PE (n = 55) were compared to trauma-exposed patients without PTSD (n = 57). We identified excessive fear in PTSD patients during acquisition and extinction before treatment compared to non-PTSD patients. At post-treatment, we examined the return of fear after extinction in PTSD patients showing high or low treatment response to PE (≥50% change in PTSD symptom severity vs. < 50%). High PE responders maintained fear extinction learning whereas low PE responders showed significant return of fear at post-treatment. These results replicate and extend previous findings of impaired extinction in PTSD and provide support for the proposed theoretical link between fear extinction and PE response.

Levels of Peripheral Circulating IL-6 and IL-10 Decrease Over Time Despite High Depression Burden in PTSD Patients.

BackgroundPatients with combined depression symptoms and post-traumatic stress disorder (PTSD) often exhibit high levels of circulating inflammatory biomarkers as either a cause or consequence of their disease. We aimed to investigate how cytokines and depression symptoms develop with one-year follow-up and compare them with non-PTSD patients.MethodsThe study had a longitudinal design with one-year follow-up measurements in an inpatient treatment setting at a psychiatric center in Norway. PTSD diagnoses were set using the Mini International Neuropsychiatric Interview (MINI). The first three measurements were at baseline (T0), halfway (T1) and at discharge (T2) from a 12-week main stay, followed by a final measurement one year after discharge (T3). Serum blood samples were collected on all four occasions. The Beck Depression Inventory-II (BDI-II) was administered at T0, T2 and T3.ResultsLevels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in PTSD patients were higher than in patients without PTSD at T0 (p = 0.005 and 0.042). The PTSD patients had a higher average level of IL-10 across all four measurements (B = 1.62, Standard Error (SE) = 0.78, p = 0.037). The IL-10 levels in PTSD patients declined from T0 to T3 (p = 0.039). The PTSD patients were more depressed than non-PTSD patients at T3 (p = 0.019).ConclusionsThe levels of IL-10 and IL-6 in PTSD patients more closely resembled the levels in non-PTSD patients at one-year follow-up, despite level of depression being unchanged in the PTSD patients. This calls into question the close relationship between level of circulating cytokines and depressive symptoms, at least in PTSD patients. Further research is needed to investigate what appears to be a complex relationship between immune markers and depression in patients with PTSD.

S608 Intentional Foreign Body Ingestion and Post-Traumatic Stress Disorder: A Review of Case Reports, Endoscopic Outcomes, and Interdisciplinary Management

Introduction: This study endeavors to fill the knowledge gap concerning deliberate foreign body ingestion (DFBI) in relation to psychiatric disorders. It concentrates on DFBI among adults diagnosed with post-traumatic stress disorder (PTSD) regarding types of foreign body (FB) ingested, motivation for DFBI, and outcomes of endoscopic FB retrieval. Methods: A review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO ID: 261785) was performed, searching electronic bibliographic databases from January 1, 2015 to June 1, 2021. Case reports written in English detailing endoscopic findings of DFBI among adults (≥18 years) were included. Articles without the number and type of items deliberately ingested were excluded. Eligible studies were assessed using the Joanna Briggs Institute critical appraisal tool. Results: Of the 55 included case reports, the 5 PTSD patients (9%) were older (μ age: 41.60 vs 34.16 years, p=0.15), less predominantly male (M:F Ratio: 1.5:1 vs 1.75:1, p=0.56), reported less abdominal pain presentations (40% vs 46%, p=0.40), and had a higher average of concomitant psychiatric conditions (μ=3 vs 1, p< 0.01), than the 55 non-PTSD patients. PTSD patients ingested more items (μ=34.8 vs 7.74, p< 0.05); specifically more large paper (μ=0.2 vs 0, p< 0.01), large wood (μ=2.8 vs 0.04, p< 0.01), small metal (μ=14 vs 0.34, p< 0.01), sharps/blades (μ=12.4 vs 1.32, p< 0.05), batteries (μ=5.4 vs 0.48, p< 0.01), than those without PTSD. The primary reasons for ingestion for both PTSD and non-PTSD patients included prior history of repeated DFBI [n=3 (60%) vs n=18 (36%), p=0.15, respectively] and suicidality (n=1 (20%) vs n=9 (18%), p=0.45, respectively]. PTSD patients had a higher average success rate of endoscopic removal (without need for post-endoscopic surgery) than non-PTSD patients (μ=1 vs 0.66, p=0.12), as well as reported use of interdisciplinary management (μ=1 vs 0.82, p=0.31). Though there was little difference in mean number of total interdisciplinary referrals made (μ=1.8 vs 1.3, p=0.28), the most common referrals were to psychiatry (47%) and gastroenterology (33%). Conclusion: In DFBI cases of patients with PTSD, a high index of suspicion is required with regards to presentation, type of FB ingested, and reason for ingestion. Further research is needed to determine if PTSD or interdisciplinary management are factors for successful endoscopic FB removal and surgery should endoscopy fail.

How does a diagnosis of PTSD add to resource utilization in Florida emergency rooms?

The objective of this analysis was to determine the added patient care time and cost associated with an incidental diagnosis of Post-Traumatic Stress Disorder (PTSD) in Florida emergency departments (ED) in Florida, United State of America. The analysis used the all-inclusive ED data from the Florida Agency for Health Care Administration, which reports patient demographic characteristics, diagnoses, location, and disposition. Facility characteristics were compiled from the Hospital Financial dataset published by the same agency. The latter data set allowed calculation of a cost-to-charge ratio for each facility to derive an estimate of the patient care cost. ED patient cases with PTSD (n = 83,346) were matched to controls using an exact neighbor algorithm based on the principal reason for the ED visit, age, gender, race, ethnicity, insurance status and type, and geographic region. In addition to the variables used for matching controls to cases, the analysis used multiple variable regression to control for additional variation based on facility characteristics and physiologic condition. Finally, the model included county fixed effects to the model to further account for the influence of facility and geographic factors. The results show that patients with PTSD spent significantly more time on average in the ED (X minutes). However, patient care facility costs did not change significantly compared to non-PTSD patients. Visit time and costs differed significantly based on demographic characteristics, insurance type and status, preexisting comorbidities, and hospital type. While direct ED related costs do not rise with a PTSD diagnosis, longer visit times imply increased resource use.

Combining Deep Learning and Graph-Theoretic Brain Features to Detect Posttraumatic Stress Disorder at the Individual Level.

Previous studies using resting-state functional MRI (rs-fMRI) have revealed alterations in graphical metrics in groups of individuals with posttraumatic stress disorder (PTSD). To explore the ability of graph measures to diagnose PTSD and capture its essential features in individual patients, we used a deep learning (DL) model based on a graph-theoretic approach to discriminate PTSD from trauma-exposed non-PTSD at the individual level and to identify its most discriminant features. Our study was performed on rs-fMRI data from 91 individuals with PTSD and 126 trauma-exposed non-PTSD patients. To evaluate our DL method, we used the traditional support vector machine (SVM) classifier as a reference. Our results showed that the proposed DL model allowed single-subject discrimination of PTSD and trauma-exposed non-PTSD individuals with higher accuracy (average: 80%) than the traditional SVM (average: 57.7%). The top 10 DL features were identified within the default mode, central executive, and salience networks; the first two of these networks were also identified in the SVM classification. We also found that nodal efficiency in the left fusiform gyrus was negatively correlated with the Clinician Administered PTSD Scale score. These findings demonstrate that DL based on graphical features is a promising method for assisting in the diagnosis of PTSD.

Evolution of post-traumatic stress disorder and patient reported-outcomes during the COVID-19 pandemic among cancer patients of the French longitudinal COVIPACT study.

12123 Background: Sudden COVID-19 pandemic has enforced social restrictions across the globe, including social distancing, curfews and total lockdowns, which persist in many parts of the world. Beyond these measures, cancer patients have faced up to the threat of the risk of severe COVID-19 infections and the adaptations of medical oncology practices, with potential impact on their psychological well-being. We aimed to follow Post-Traumatic Stress Disorder (PTSD) symptoms and other Patient-Reported Outcomes (PROs) over this period among cancer patients from the French COVIPACT study. Methods: The COVIPACT study (NCT04366154) included patients with solid/hematologic malignancy receiving medical treatment during the first lockdown in outpatient departments of two cancer centers. Patients were asked to fulfill validated questionnaires on PTSD symptoms (IES-R), insomnia (ISI), quality of life (FACT-G) and cognition (FACT-Cog) at baseline (M0, first lockdown, Apr/May 2020), 3 months (M3, post-lockdown, Jul/Aug 2020) and 6 months (M6, second lockdown, Oct/Nov 2020). PTSD was defined as an IES-R score ≥33 and moderate/severe insomnia as an ISI score ≥15. Higher values on the FACT-G (range 0-108) and FACT-Cog (PCI subscale range 0-72) indicated better quality of life and cognition, respectively. Changes in PROs over time were assessed using mixed models for repeated measures. Results: Among the 734 patients included in COVIPACT, 579, 347 and 328 completed the questionnaires at M0, M3 and M6, respectively: median age, 64 years, 72% women, 59% metastatic status. Patients were mostly treated for breast (44%), lung, head and neck (20%), digestive (16%) and gynecologic cancers (11%). We observed a J-shaped evolution of PTSD over time, affecting 21.2% of patients during the first lockdown, 13.6% the post-lockdown and 23.6% during the second lockdown (p for time &lt; 0.001). Moreover, patients reported linear deterioration of cognitive function over follow-up (p &lt; 0.001). No change was observed in any dimension of quality of life (p for time = 0.06). 24.3%, 27.1% and 28.1% of the patients reported insomnia at M0,M3 and M6 (p for time = 0.35). At each time, PTSD was associated with more insomnia, worst quality of life and cognitive complain. At all the times, ≥50% of patients with PTSD reported insomnia compared to ≤23% in non-PTSD patients (p &lt; 0.001). In addition, there was a clinically significant difference of ≥16 points on the FACT-G and ≥8 points on the FACT-Cog PCI between PTSD and non-PTSD patients (p &lt; 0.001) at the all times. Conclusions: More than 20% of patients have developed PTSD during the different periods of lockdown, with strong association with poor quality of life, cognitive complain and insomnia. Psychosocial support promoting emotional resilience should be largely offered to cancer patients to prevent and/or reduce PTSD. Clinical trial information: NCT04366154.

Persistent level of mental distress in PTSD patients is not reflected in cytokine levels 1 year after the treatment.

Cross-sectional data show that post-traumatic stress disorder (PTSD) patients often have increased levels of circulating inflammatory markers. There is, however, still a paucity of longitudinal studies with long follow-up times on levels of cytokines in such patients. The current study assesses patients with and without PTSD diagnosis 1 year after discharge from inpatient treatment. Patients in treatment for serious non-psychotic mental disorders were recruited at the beginning of their treatment stay at a psychiatric centre in Norway. Ninety patients submitted serum samples and filled out the Hopkins Symptom Checklist-90 Revised Global Severity Index (HSCL-90R GSI) questionnaire during their mainstay and at a follow-up stay 1 year after discharge. Of these patients, 33 were diagnosed with PTSD, 48 with anxiety, depression, or eating disorder, while 9 patients had missing data. The patients were diagnosed using the Mini-International Neuropsychiatric Interview (MINI). At the follow-up stay (T3), PTSD patients had higher levels of GSI scores than non-PTSD patients (p = 0.048). These levels were unchanged from the year before (T2) in both groups. The levels of circulating cytokines/chemokine did not differ between the PTSD and non-PTSD patients at T3. At T2, however, the PTSD and non-PTSD groups exhibited different levels of interleukin 1β (IL-1β) (p = 0.053), IL-1RA (p = 0.042), and TNF-α (p = 0.037), with the PTSD patients having the higher levels. Despite exhibiting different mental distress scores, the PTSD and non-PTSD patients did not differ regarding levels of circulating inflammatory markers at 1-year follow-up.

The Association Between Brain Volumes and Posttraumatic Stress Disorder in Intensive Care Unit Survivors: A Preliminary Study.

IntroductionMillions of Americans are admitted to the intensive care unit (ICU) per year. Many survivors of the ICU will experience posttraumatic stress disorder (PTSD); although volumetric hippocampal and amygdala studies have been conducted in other trauma survivors (i.e., veterans), the association between PTSD symptoms and hippocampal and amygdala volumes in ICU survivors has not been described. We hypothesize that the severity of posttraumatic stress symptoms in ICU survivors is associated with lower volumes of both the hippocampus and amygdala at 3 and 12 months.MethodsSecondary analysis of the VISIONS study, a prospective sub-study of the BRAIN-ICU cohort, which included survivors of critical illness. The PTSD Checklist Specific was used at 3 and 12 months to evaluate the ICU as a traumatic experience. A Philips Achieva 3T MRI scanner was used to scan patients at both discharge and 3 months. To compare median brain volumes at discharge and 3 months for those with and without PTSD symptomatology, we used a Kruskal–Wallis (KW) test.ResultsAt 3 month follow up, three patients had PTSD symptomatology and N = 1 at 12 month follow up. There was no difference between median brain volumes (hippocampus or amygdala) between individuals with PTSD symptomatology at either 3 or 12 months (p-values > 0.05).DiscussionAlthough our study did not reveal significant differences in brain volumes between PTSD patients and non-PTSD patients, sample size was a major limitation and larger scale studies should be undertaken to elucidate possible neurobiological markers of PTSD in ICU survivors.

Traumatic Events and Substance Use Disorders in Adolescents.

ObjectivesAdolescents with substance use disorders (SUD) frequently report traumatic events (TEs) and symptoms of post-traumatic stress disorder (PTSD). This study aimed to assess whether lifetime prevalence rates of TEs and PTSD are related to SUD severity in adolescent psychiatric patients.MethodsWe analyzed N = 114 self-reports of treatment-seeking German adolescents aged 12 to 18 years, who visited a specialized SUD outpatient unit. Standardized questionnaires were applied to assess SUD severity, the number of TEs and DSM-IV PTSD criteria.ResultsPatients fulfilling PTSD criteria (28% of the total sample) had a higher Drug Use Disorders Identification Test (DUDIT) score compared to non-PTSD patients with TEs (p <.001), and compared to adolescents without TEs or PTSD (p = .003). Additionally, SUD severity was positively associated with the number of TEs and the number of intrusion, hyperarousal, and avoidance symptoms (all r = .33 to.48, all p <.01).DiscussionAdolescent patients with SUD reported 3-times higher rates of TEs, and a 5-time higher prevalence of PTSD following TEs, than the general adolescent population. Adolescent SUD patients with PTSD reported more severe substance use problems than patients without PTSD—regardless of previous TEs. Longitudinal studies are needed in order to investigate the temporal relationship between TEs, PTSD and SUD.

4417 Association between Brain Volumes and Posttraumatic Stress Disorder in Intensive Care Unit Survivors

OBJECTIVES/GOALS: To explore the severity of posttraumatic stress disorder (PTSD) symptoms in association with hippocampal and amygdala volumes in ICU survivors. We hypothesize that the severity of posttraumatic stress symptoms in ICU survivors is associated with lower volumes of both the hippocampus and amygdala. METHODS/STUDY POPULATION: Secondary analysis of the VISIONS study, a prospective sub-study of the BRAIN-ICU cohort, which included survivors of critical illness. Patients were screened for preexisting PTSD before discharge. The PTSD Checklist Specific (PCL-S) was used at 3 and 12 months to evaluate the ICU as a traumatic experience. A score of &gt;30, indicated significant symptoms of PTSD. A Philips Achieva 3T MRI scanner was used to scan patients at both discharge and 3-month follow-up. To compare median brain volumes at discharge and 3 months for those with and without significant PTSD symptomatology (PCL-S ≥30) at 3 and 12 months, we used a Kruskal-Wallis (KW) equality-of-populations rank test. RESULTS/ANTICIPATED RESULTS: The median age for our sample was 58.5 (52.6, 63.7). One-third of the sample was female, and 90% were Caucasian. Fifty-seven percent of individuals (N = 12) had at least one prior mental health diagnosis, with two having a prior history of PTSD. One third of individuals experienced delirium during their critical illness. At 3-month follow up, there were three patients with PTSD symptomatology and one at 12-month follow up. Median brain volumes (hippocampus or amygdala) did not differ between individuals with or without PTSD symptomatology at either 3 or 12 months (p-values for all tests &gt;0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Although our study did not reveal significant differences in brain volumes between PTSD patients and non-PTSD patients, sample size is a major limitation and larger scale studies should be undertaken to elucidate possible neurobiological markers of PTSD in ICU survivors. CONFLICT OF INTEREST DESCRIPTION: Dr. Wilson would like to acknowledge salary support from the Vanderbilt Faculty Research Scholars Program (1KL2TR002245), HL111111 and GM120484. Drs. Ely and Jackson as well as Mrs. Kiehl all receive funding for their time working on this investigation from AG035117 and HL111111. Dr. Ely would additionally like to acknowledge salary support from the Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC). Dr. Ely will also disclose additional funding for his time from AG027472 and having received honoraria from Orion and Hospira for CME activity; he does not hold stock or consultant relationships with those companies. The authors would like to acknowledge the following: this work was conducted in part using the resources of the Center for Computational Imaging at Vanderbilt University Institute of Imaging Science and the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN, and study data were collected and managed using REDCap electronic data capture tools hosted at Vanderbilt University.

Cytokine concentrations are related to level of mental distress in inpatients not using anti-inflammatory drugs.

Cross-sectional data show elevated levels of circulating cytokines in psychiatric patients. The literature is divided concerning anti-inflammatory drugs' ability to relieve symptoms, questioning a causal link between inflammatory pathways and psychiatric conditions. We hypothesised that the development of circulating cytokine levels is related to mental distress, and that this relationship is affected by the use of anti-inflammatory drugs. The study was a longitudinal assessment of 12-week inpatient treatment at Modum Bad Psychiatric Center, Norway. Sera and self-reported Global Severity Index (GSI) scores, which measure psychological distress, were collected at admission (T0), halfway (T1) and before discharge (T2). Other variables known to distort the neuroimmune interplay were included. These were age, gender, diagnosis of PTSD, antidepressants and anti-inflammatory drugs. A total of 128 patients (92 women and 36 men) were included, and 28 were using anti-inflammatory medication. Multilevel modelling was used for data analysis. Patients with higher levels of IL-1RA and MCP-1 had higher GSI scores (p = 0.005 and p = 0.020). PTSD patients scored higher on GSI than non-PTSD patients (p = 0.002). These relationships were mostly present among those not using anti-inflammatory drugs (n = 99), with higher levels of IL-1RA and MCP-1 being related to higher GSI score (p = 0.023 and 0.018, respectively). Again, PTSD patients showed higher GSI levels than non-PTSD patients (p = 0.014). Cytokine levels were associated with level of mental distress as measured by the GSI scores, but this relationship was not present among those using anti-inflammatory drugs. We found no association between cytokine levels and development of GSI score over time.

Stochastic resonance as a proposed neurobiological model for Eye Movement Desensitization and Reprocessing (EMDR) therapy

EMDR therapy is recommended in several guidelines in the International field of psychological trauma. The dual attention stimuli/alternating bilateral stimulation (DAS/ABS) element of EMDR therapy has no proposed mechanism of action agreed upon, which explains the rapid shifts in cognitions and dysfunctional traumatic memory networks that are central to its observable efficacy. This paper discusses an innate, biological mechanism found in biological systems, including the human nervous system that may explain the efficacy of DAS/ABS. This mechanism is stochastic resonance (SR). SR is observed to make unintelligible, subthreshold signals intelligible and facilitates signal transmission. It provides a potential mechanism for discrimination and the selective focusing of attention, which are important factors in effective psychotherapy for the psychologically traumatised individual. The body/mind complex aims to achieve the functional encoding of memories in the neocortex and a key structural crossroads in this process is the thalamus. Activity in the thalamus is decreased in Post-Traumatic Stress Disorder (PTSD) compared to non-PTSD patients and a form of ‘gating’ is known to occur at the thalamic level. This ‘gating’ is adaptive and it is postulated to protect the higher neocortical systems in times of trauma. Although the model is initially somewhat counterintuitive, Stochastic Resonance; a form of random ‘noise’, can be considered ‘helpful randomness’ and when present in the thalamus SR can help filter and control sensitivity to incoming signals; helping to discriminate what is communicated. Naturally occurring SR is normally present as a result of descending cortico-thalamic activity, but appears attenuated as a result of exposure to trauma. The view of ‘noise’ in the current era of cell phones and High Definition is generally negative with science going to significant lengths to clean up signals: i.e. removing noise from them. We do not want white noise in our music or during our cell phone calls. However, some researchers invite us to consider that not all noise is bad and the downward cortico-thalamic ‘noise’ is an example of this category of ‘helpful noise’. This paper will discuss the potential role of SR, as the mechanism by which DAS/ABS generates a random (stochastic) signal, facilitating a return to functional memory processing, where there is a lack of naturally occurring noise from the descending cortico-thalamic connections because of exposure to trauma. Modelling the mechanism as SR will facilitate further study into EMDR therapy and this will hopefully encourage perspicacity, where there has previously been derision.

Heart Rate Assessment for Posttraumatic Stress Disorder Symptoms among Military Veterans: A Narrative Literature Review

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition affecting as much as 20% of the returning veterans from the current wars in Afghanistan and Iraq (Ramchand et al., 2010). Due to its prevalence, assessment and intervention methods for PTSD symptoms among veterans are timely to ensure veterans’ faster recovery and their reintegration into society. A narrative review of literature was conducted to examine the literature on techniques and methods for detection and measurement of PTSD symptoms. Relevant reviews and seminal papers associated with psychophysiological measurements with emphasis on heart rate, the prevalence of PTSD in military veterans, and detection of PTSD were included. Psychophysiology involves the non-invasive recording of biological processes simultaneously (Pole, 2007). The measures that were found to be reliably related to PTSD are: (1) higher resting heart rate; (2) larger heart rate responses to standardized trauma cues; and (3) for idiographic cues facial muscle electromyography (EMG) and heart rate responses (Pole, 2007). Studies based on heart rate found that there were five beats per minute (bpm) increase in resting heart rates for combat veterans who suffer from PTSD compared to those who were not diagnosed (Beckham et al., 2000, Woodward et al., 2009). Buckley et al. (2004) found that for a mixed population (veterans and civilians) PTSD patients had a resting heart rate increase of 6.6 bpm compared to non-PTSD patients while adjusting for covariates. The exact mechanisms of how stress affects heart rate are not well-known; however, it is possible to observe stressful events and relate these to physiological changes in heart rate that can be measured using modern sensors (Andreoli et al., 2010). In the literature, heart rate is analyzed using statistical, geometric, frequency domain, time-frequency and non-linear feature analysis (Acharya et al., 2006). Non-linear features have been developed to quantify the dynamics of heart rate fluctuations. These include approximate entropy, Detrended Fluctuation Analysis (DFA), Lyapunov exponent, Recurrence Plots (RPs) and Correlation Dimension (CD) (Pincus, 1991; Huikuri et al., 2000; Acharya et al., 2004; Acharya et al., 2006). Our synthesis resulted in identification of three research gaps. Heart rate analysis has shown promise to link PTSD symptoms to differences in PTSD and non-PTSD subjects (Pole, 2007) but a characterization of PTSD symptoms from heart rate data seems to remain a research gap. While continuous monitoring of physiological parameters is gaining momentum, this particular method has not been studied to infer key characteristics associated with PTSD among military veterans. Continuous monitoring might be able to highlight muted response to startle or treatment. There is also a research gap in the assessment of heart rate accelerations and decelerations in response to specific PTSD symptoms (Khanade et al., 2017). The investigation into accelerations/decelerations associated with PTSD hyper-arousal triggers might have a potential to detect hyper-arousal instantaneously and would shed light on trigger-specific interventions to reduce harmful effects of PTSD triggers in a timely manner. In addition, most studies were conducted to observe differences among PTSD and non-PTSD populations. More work is warranted to focus on PTSD patients in isolation to explain variety of triggers and their specific physiological reactions.

PTSD patients show increasing cytokine levels during treatment despite reduced psychological distress.

BackgroundA reciprocal relationship between activated innate immune system and changes in mood and behavior has been established. There is still a paucity of knowledge on how the immune system responds during psychiatric treatment. We aimed to explore circulating cytokines and assess psychiatric symptom severity scores during 12 weeks of inpatient psychiatric treatment.MethodsThe study was a longitudinal assessment of 124 patients (88 women and 36 men) in treatment at Modum Psychiatric Center, Norway. The patient sample comprised a mixed psychiatric population of whom 39 were diagnosed with posttraumatic stress disorder (PTSD). Serum blood samples for cytokine analysis and measures of mental distress using Global Severity Index were collected at admission (T0), halfway (T1), and before discharge (T2). Other factors assessed were age, gender, and the use of antidepressants and anti-inflammatory drugs. Multilevel modeling was used for longitudinal analyses to assess the repeated cytokine samples within each patient.ResultsOverall level of IL-1RA was higher in PTSD patients when compared to those without PTSD (P=0.021). The level of IL-1β, MCP-1, and TNF-α increased over time in PTSD compared to non-PTSD patients (P=0.025, P=0.011 and P=0.008, respectively). All patients experienced reduced mental distress as measured by self-reported Global Severity Index scores. Stratified analysis showed that PTSD patients who used anti-inflammatory drugs had higher levels of IL-1β (P=0.007) and TNF-α (P=0.049) than PTSD patients who did not use such drugs.ConclusionThe study indicates that traumatized patients may have a distinct neuroimmune development during recovery. Their activated immune system shows even further activation during their rehabilitation despite symptom reduction.

PTSD, Pain Medication and Addiction of Refugees in Iraq

The relationship of pain medication uses with posttraumatic stress disorder (PTSD) diagnosis was investigated among a sample of 213 Kurdish outpatients in refugee camps in Kurdistan-Region in Northern Iraq. One hundred twenty-four (58%) of the participants met DSM-V PTSD criteria. Those with PTSD had significantly higher use of pain medication (82%), as compared with non-PTSD patients (47%). Female (54%) with a Posttraumatic Stress Disorder had higher use than male (4%) of pain medication. For the effective treatment of trauma in relation to chronic pain and medication use, it is necessary to have a multi-modal, interdisciplinary and culture-sensitive approach when treating.

Improving PTSD Symptoms and Preventing Progression of Subclinical PTSD to an Overt Disorder by Treating Comorbid OSA With CPAP.

Obstructive sleep apnea (OSA) and posttraumatic stress disorder (PTSD) are common in United States veterans. These conditions often coexist and symptoms overlap. Previous studies reported improvement in PTSD symptoms with continuous positive airway pressure (CPAP) therapy for comorbid OSA but its effect has not been assessed in a non-PTSD cohort. We have prospectively assessed the effect of CPAP therapy on clinical symptom improvement as a function of CPAP compliance levels among PTSD and non-PTSD veterans. Veterans in whom OSA was newly diagnosed were enrolled in our study (n = 192). Assignment to PTSD and non-PTSD cohorts was determined by chart review. Each patient completed the military version of the PTSD Checklist (PCL), Epworth Sleepiness Scale (ESS), and reported nightmare frequency (NMF) at baseline and 6 months after CPAP therapy. CPAP adherence was objectively documented from machine compliance data. We had complete data for 177 veterans (PTSD n = 59, non-PTSD n = 118) for analysis. The mean ages were 51.24 years in the PTSD cohort and 52.36 years in the non-PTSD cohort (P = .30). In the PTSD cohort, the mean total PCL score (baseline = 66.06, post-CPAP = 61.27, P = .004, d = -0.34) and NMF (baseline = 4.61, post-CPAP = 1.49, P = .0001, d = -0.51) decreased after 6 months of CPAP treatment. Linear regression analysis showed that the CPAP compliance was the only significant predictor for these changes among veterans with PTSD (PCL score: P = .033, R2 = .65; NMF; P = .03, R2 = .61). Further analysis by CPAP compliance quartiles in this cohort (Q1 = 0% to 25%, Q2 = 26% to 50%, Q3 = 51% to 75%, Q4 > 75%) revealed that mean total PCL score declined in Q2 (change = -3.91, P = .045, d = 0.43), Q3 (change = -6.6, P = .002, d = 0.59), and Q4 (change = -7.94, P = .037, d = 0.49). In the non-PTSD cohort, the PCL score increased despite CPAP therapy in lower CPAP compliance quartiles Q1 (change = 8.71, P = .0001, d = 0.46) and Q2 (change = 4.51, P = .046, d = 0.27). With higher CPAP compliance (in Q3 and Q4) in this cohort, the mean total PCL scores slightly improved with CPAP but they were not statistically significant (P > .05). CPAP treatment reduces total PCL score and NMF in veterans with PTSD and OSA. Those with overt PTSD respond to even lower CPAP compliance, whereas non-PTSD patients require higher compliance to achieve any symptom improvement. Poor CPAP compliance results in increased PCL score in non-PTSD veterans and may lead to overt PTSD if the OSA remains undertreated. A commentary on this article appears in this issue on page 1121.