PTSD Patients Research Articles

The effect of TMS on the extinction of fear memory in PTSD patients

PTSD is a common consequence of individuals' exposure to life-threatening traumatic events, such as traffic accidents. It is closely related to fear memories, leading to trauma recurrence, avoidance behavior, impaired function, and emotional distress. In healthy people, memories of terror fade automatically after they are formed, but people with PTSD are less able to fade memories of terror by themselves. Experiments have shown that humans can eliminate the horrible memories formed in the hippocampus and amygdala by eliminating memory training, and TMS can enhance the learning and consolidation of fading memories. The purpose of this study was to test whether TMS could eliminate the horrible memories of traffic accidents. The results show that According to the correlation degree analysis of traffic accident related pictures, the first, second, seventh and eighth pictures with significant differences were excluded. Rule out pairs 4 and 5 according to the neutral rule. Rule out the sixth pair of pictures according to the same property principle. According to the experimental data, the subjects successfully combined traffic-related pictures with fear in the acquisition stage, changed the fear memory association in the extinction stage, and showed no significant difference in CS+ and CS- in the arousal stage. It is proved that TMS can be used to fade the memory of traffic fear, and TMS stimulation of F3 and F4 can both produce the effect of fading the memory of traffic fear. TMS can promote the treatment of PTSD patients caused by traffic accidents. This study can provide references for the treatment of PTSD patients caused by other types of horrible memories and the application of TMS technology. get date from 2 groups analyze data from NFE group in acquisation check if result is proi__ned analyze data from NFE group in extinction phase analyze resulted trend analyze data from recall phase fiom 2 goups compare and draw conclusion Figure 1 First Secord day day acquisition 20CS+(P)+US 10min extinction recall 20CS+(P) 40CS+(T+P) 40CS+P 40CS-(P) 40CS-(T +P) 40CS-P acquisition 20CS+(P)+US 10min extinction recall 20CS+(P) 40CS+P 40CS+P 40CS-(P) 40CS-P 40CS-P Figure 2

Why Can’t We See It?

ABSTRACT The relevance of a patient’s experience of physical punishment in childhood may be obscured and difficult to acknowledge for both patient and analyst. This paper illustrates my own struggle with the issue by presenting excerpts of my work with an adult analytic patient, children in a mental health clinic, and PTSD patients in the Veterans Administration system. In the discussion that follows I demonstrate how the psychoanalytic concept of disavowal can be useful in expanding our ability to engage in meaningful discussions with our patients regarding this issue.

A Study on the Association between Patients with Post-Traumatic Stress Disorder in Li and Han Ethnic Groups in Hainan Province and DNA Methylation of Brain-Derived Neurotrophic Factor Genes

Objective: To explore the pathogenesis of PTSD in the brain-derived neurotrophic factor (BDNF) gene methylation of patients with posttraumatic stress disorder (Posttraumatic Stress Disorder, PTSD) in Hainan Province, the relationship between the influence of BDNF gene methylation and the influence of PTSD. Methods: A case-control study method was adopted, strictly in accordance with DSM-IV and PTSD diagnosis, and 150 Li PTSD patients matched with gender and age of 300 Han PTSD patients were selected as the research objects. The peripheral venous whole blood of the subjects was drawn, genomic DNA was extracted, modified with bisulfite, and directly sequenced to quantitatively detect the methylation status of the CpG island in the promoter region of brain-derived neurotrophic factor (BDNF). Results: The results showed that the methylation levels of CPGl, CPG2, CPG3, CPG4, CPG5, CPG6, CPG7, CPG9, CPGl2, CPGl3, CPGl4, CPGl5, CPGl6, CPGl7, and CPGl8 in THE BDNF promoter were significantly different between the HAN PTSD group and the Li PTSD group (P Conclusion: It is suggested that CPG methylation in the promoter region of BDNF gene is closely related to patients with PTSD. There is a statistical difference in the level of CpG methylation in the promoter region of BDNF gene in PTSD between Li and Han ethnic groups in Hainan Province. CpG methylation in the promoter region of BDNF gene may be used as a biomarker for the diagnosis of PTSD.

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.

A qualitative analysis of the quality of social and marital support for PTSD victims

In recent years, many authors have written on the importance of analyzing social support when it comes to understanding PTSD patients. However, the effects of important aspects of the social support construct itself, such as the source of support and its underlying psychosocial processes, remain relatively unexamined. Using a qualitative design, this study sought to explore social support processes between PTSD patients and their relatives. More specifically, thematic and conversational analysis were performed on filmed interactions between 48 PTSD patients and an accompanying person (AP) of their choice. Results indicated that female PTSD patients generally presented a higher frequency of negative interactions than male diagnosed with PTSD. Moreover, couples generally experienced more negative social support compared to non-couples. Finally, it was found that the length of the relationship as well as the onset of the PTSD (before or after the beginning of the relationship) influenced the quality of the interactions for couples in this sample. To our knowledge, this study is one of the few qualitative research that has been made on interactions between PTSD patients and their relatives. This study also offers an innovative point of view on the social processes underlying marital and social support, such as the impact of the length and moment of apparition of romantic relationships on the quality of support offered.

Psychopathology and Quality of Life in Traumatized or Victimized Underage Individuals as Factors for Forensic Multilevel Assessment-A Pilot Investigation.

Background: Psychological sequels to criminal violence can be long lasting and severe. They are in many countries not sufficiently considered in court cases as an important circumstance that could be used to assess the severity of the crime, also guiding redress, compensation, and rehabilitation of the victim, and—in children—child custody considerations. So far, the focus of forensic assessment has often been limited to diagnostic categories, especially “posttraumatic stress disorder” (PTSD), a diagnosis that presently is subjected to rapidly changing definitions both in and between diagnostic systems. Other indicators such as quality of life (QoL) might be of equal importance as compared to clinical or research diagnostic categories to understand and evaluate the impact of a crime and the amount of help needed and, in the legal context, redress to be asked. Symptoms might differ depending on the crime encountered.Objective and Methods: QoL and general symptom patterns including a PTSD diagnosis were assessed in a group of 10- to 17-year-old minors with (n = 33) and without (n = 49) PTSD diagnosis who all had experienced sexual abuse, physical abuse, death of a parent, or their parents’ divorce, using standardized diagnostic instruments.Results: PTSD patients reported a significantly lower QoL than non-PTSD controls. Reported symptom patterns with potential impact on life, such as intrusive thoughts, differed between the victims of different crime types, with the highest rates of both intrusive symptoms and combined symptom profile in victims of sexual abuse. Data indicate that the changes between older and present criteria and between DSM and recently published ICD 11 might help identify different groups and symptom profiles.Conclusion: Specific trauma-related symptom profiles integrating the type of crime encountered and its individual impact on QoL may help improve future forensic assessment and guide compensation and rehabilitation plans. Carefully designed studies are now needed to further explore the use and forensic usability of complex indicators and the impact of violence in different forensic settings.

Exploring criminal responsibility of PTSD patients; findings from a survey in Chinese Mainland courts

BackgroundThe Wenchuan Earthquake in Sichuan Province is China's deadliest natural disaster in a generation; after such disturbance, a kind of mental illness named post-traumatic stress disorder (PTSD, also called delayed psychogenic reaction) raises concern in Mainland China, but probably not rapidly sufficient. Different from that in the USA, earthquake is both the reason and focus of PTSD research in China. MethodsIn order to find out the relationship between the PTSD defense and criminal responsibility in Mainland China, the authors decided to use certain academic tools and analysis judicial decisions (816 cases). The authors identified key information from government official websites. ResultsData demonstrated that research regarding PTSD increases considerably after the Wenchuan earthquake in 2008. However, data also showed that Chinese courts are hesitant in accepting PTSD as a mental defense for criminals, despite relevant existing rules. Some legal ambiguities, such as lack of procedures or instructions for the connection between diagnosis and judgment, can be observed when courts encounter criminals with PTSD. ConclusionsPTSD patients occur in all races, classes, religions, and nationalities and some would unfortunately be criminals. This pattern reveals concern for the boundary between the reasonable use and abuse of PTSD in view of medico-legal expertise practice. Expert testimony or opinion cannot replace the judges’ decision. Chinese courts should learn from the American Bar Association and accept the three-part analysis for forensic consideration of PTSD. Further details regarding the regulations for resolving the criminal responsibility of PTSD patients should be obtained.

109. Mega-Analysis of Cortical Morphometric Differences Between PTSD Patients and Non-PTSD Controls

Multiple studies have reported morphometric abnormalities in PTSD, but small sample size of individual studies has limited statistical power to detect smaller scale changes. Whole cortex mega-analyses combining regional analyses and higher discrimination vertex analyses in large numbers of subjects provide an opportunity to overcome small sample limitations.

O40. PTSD Augmented Psychotherapy With Ketamine (KPE) - First Results

Augmenting prolonged exposure (PE) with pharmacotherapy has been suggested as a promising solution to address treatment-resistant PTSD and high dropout rates. Ketamine has been shown to have rapid-acting effects on treatment resistant depression following single infusion and with neurogenesis, that may promote new learning. We present first results of ketamine augmentation of intensive 7-day-PE (KPE) for PTSD patients.

Inflammation in PTSD is a consequence of dysregulated WNT signaling orchestrated by long non-coding RNA LINC00926 and lysine methyltransferase MLL1

Abstract Posttraumatic Stress Disorder patients experience chronic inflammation. It is not known whether immune dysregulation causes PTSD or the psychiatric imbalance occurs first. Moreover, little is known about the molecular mechanisms involved in the immune dysregulation. Our past work indicates the involvement of epigenetic mechanisms such as histone methylation in the regulation of inflammation in PTSD. By employing RNA-Seq, we identified upregulated expression of WNT10B and LINC00926 in the PBMCs of PTSD. Thus, we hypothesized that LINC00926 overexpression in PTSD results in increased H3K4me3 (gene activating histone methylation) around the promoter of WNT10B leading to its upregulation which in turn, regulated the elevated expression of inflammatory cytokines like IFNg and IL17. Thus, we first confirmed the interaction between LINC00926 and the histone H3K4 methyltransferase, MLL1. Then, by in vitro knockdown of LINC00926 we confirmed lowered expression of WNT10B implying that the interaction between LINC00926 and MLL1 possibly leads to increased H3K4me3 on WNT10B promoter and thereby its upregulation. Following this, we confirmed increased H3K4me3 around WNT10B promotor of PTSD patients by ChIP-Seq. Finally, we confirmed that upregulated WNT10B indeed contributed to the elevated expression of IFNg and IL17. In conclusion, our data implies that upregulation of LINC00926 in PTSD leads to inflammatory state by a mechanism that involves interaction with MLL1 resulting in increased H3K4me3 around WNT10B promotor and, eventually leads to elevated expression of proinflammatory cytokines. Our report is the first to show that inflammation in PTSD is a result of altered epigenetic mechanism involving LINC00926 and WNT10B.

High cortisol awakening response in the aftermath of workplace violence exposure moderates the association between acute stress disorder symptoms and PTSD symptoms

Although a majority of people will be exposed to a traumatic event over the course of their lifespan, only a minority will develop post-traumatic stress disorder. Better understanding the factors contributing to the development of this psychopathology is of high importance and could significantly reduce the societal and human costs associated with PTSD. Acute stress disorder symptoms, which refers to clinical manifestations experienced in the aftermath of a traumatic event, have been shown to be associated with subsequent PTSD symptoms. Yet, many people who develop PTSD do not meet criteria for acute stress disorder in the first place, highlighting the need to refine the predictors of PTSD. The secretion of the stress hormone cortisol is dysregulated in PTSD patients. Whether combining clinical and biological measures in the aftermath of trauma could help to better explain subsequent PTSD symptoms remains to be tested. The current prospective study recruited 51 adults who were exposed to a traumatic event in their work setting, i.e. a psychiatric hospital. Acute stress disorder symptoms and cortisol awakening responses were assessed one to five weeks following trauma exposure (Time 1). PTSD symptoms were measured two months following trauma exposure. Results revealed a significant interaction between acute stress disorder symptoms and cortisol awakening response in predicting later PTSD symptoms. The results suggest that higher cortisol awakening response is a protective factor in that it abolishes the relationship between acute stress disorder symptoms and subsequent PTSD symptoms. These results point to the importance of considering multi-level information in the aftermath of trauma, such as clinical and biological measures, in order to better identify individuals who are at higher risk of developing PTSD.

Medical Expenses of North Korean Defectors with Post-Traumatic Stress Disorder

ObjectiveThe purpose of this study was to establish the prevalence of PTSD among North Korean defectors who visited the National Medical Center, Seoul, South Korea over a period of approximately 10 years by examining their medical records and to examine differences in the medical service usage patterns of patients with and without PTSD. MethodsData from North Korean defectors who used outpatient services at the National Medical Center during a period of 10 years and 3 months (January 1 2006 to February 28, 2016) were analyzed. The general characteristics of the defectors were analyzed by frequency analyses, and descriptive statistics were generated. Additionally, independent t-tests and chi square analyses were performed to examine differences between PTSD patients and those without PTSD. Linear regression analysis was performed to examine factors affecting the mental health of North Korean defectors suffering from PTSD. ResultsThis study assessed the correlations between PTSD, the average number of outpatient visits, and the total revenue. The regression analysis showed a relationship between PTSD and the average number of outpatient visits. There was also a correlation between PTSD and total revenue. The average number of outpatient visits was 41.8 for PTSD patients, whereas it was 33.2 for those without PTSD. The total revenue visit was 953.6 USD for PTSD sufferers and 231.1 USD for those without PTSD. ConclusionThis study found that the majority of North Korean defectors visit psychiatry departments, and that PTSD patients use outpatient services more frequently and have higher total revenue than those without PTSD. Additionally, patients with PTSD used a greater variety of medical services. Considering the high medical care expenses of North Korean defectors residing in South Korea, future investigations should examine the medical service usage patterns of such patients, especially those diagnosed with PTSD, in greater detail.

Cortisol levels in different tissue samples in posttraumatic stress disorder patients versus controls: a systematic review and meta-analysis protocol

BackgroundPosttraumatic stress disorder (PTSD) is a disorder that develops following exposure to severely stressful events. Altered cortisol secretion has been reported in PTSD; however, results have been inconsistent. Previous meta-analyses of cortisol levels in PTSD have combined results of studies that have used different tissue samples (blood, saliva, urine) for cortisol measurement and have not included newer methods of determining cortisol levels (e.g. hair samples). In this systematic review, we will synthesise evidence from studies evaluating basal cortisol levels in PTSD patients versus controls and stratify studies according to tissue type used for cortisol measurement. We will also determine whether results from different tissue types can be pooled and if any specific tissue samples have better utility in research studies on PTSD.MethodsWe will perform a systematic review of the scientific literature including all studies that have evaluated basal or baseline cortisol levels in adults with current PTSD versus controls, with and without trauma exposure. Independent reviewers will conduct searches in electronic databases (Medline, CINAHL, PTSDpubs, Web of Science, Scopus, ProQuest Dissertations & Theses A&I, ClinicalTrials.gov, and ICTRP), and additional studies will be obtained by searching the reference lists of articles. Two reviewers (LLvdH and SW) will independently conduct standardised screening, eligibility assessments, data extraction, and quality assessments before qualitative and, if appropriate, quantitative (meta-analysis and meta-regression) synthesis. Disagreements that arise at any stage will be resolved by a third reviewer (ShS).DiscussionIn line with previous reviews, we expect that cortisol levels will be lower in PTSD patients than in controls, but that patterns may vary somewhat according to the tissue sample in which cortisol is measured. This systematic review will assist in developing a better understanding of the acute and chronic patterns of basal cortisol secretion in PTSD and will inform future research.Systematic review registrationPROSPERO CRD42018091874

A Review of the Relationship Between Emotional Learning and Memory, Sleep, and PTSD.

The emotional memory and learning model of PTSD posits maladaptive fear conditioning, extinction learning, extinction recall, and safety learning as central mechanisms to PTSD. There is increasingly convincing support that sleep disturbance plays a mechanistic role in these processes. The current review consolidates the evidence on the relationships between emotional memory and learning, disturbed sleep, and PTSD acquisition, maintenance, and treatment. While disrupted sleep prior to trauma predicts PTSD onset, maladaptive fear acquisition does not seem to be the mechanism through which PTSD is acquired. Rather, poor extinction learning/recall and safety learning seem to better account for who maintains acute stress responses from trauma versus who naturally recovers; there is convincing evidence that this process is, at least in part, mediated by REM fragmentation. Individuals with PTSD had higher "fear load" during extinction, worse extinction learning, poorer extinction recall, and worse safety learning. Evidence suggests that these processes are also mediated by fragmented REM. Finally, PTSD treatments that require extinction and safety learning may also be affected by REM fragmentation. Addressing fragmented sleep or sleep architecture could be used to increase emotional memory and learning processes and thus ameliorate responses to trauma exposure, reduce PTSD severity, and improve treatment. Future studies should examine relationships between emotional memory and learning and disturbed sleep in clinical PTSD patients.

Neuroimaging Phenotypes Implicated For GWAS of PTSD Through The PGC And ENIGMA Worldwide Consortia

Here, we present the results of a large-scale neuroimaging-genetics consortium study on PTSD conducted by the Psychiatric Genomic Consortium (PGC) and Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) PTSD Working Group. Hippocampus, hippocampal subfield, and amygdala volume differences are strongly implicated in PTSD, but findings have not always been consistent. Our goal was to characterize these neuroimaging phenotypes for subsequent GWAS. We analyzed neuroimaging and clinical data from 1,868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle) in n=1,868. We assessed 11 hippocampal subfield volumes bilaterally (cornu ammonis 1 (CA1), CA3, CA4, dentate gyrus (DG), fimbria, fissure, hippocampus-amygdala transition area (HATA), molecular layer, parasubiculum, presubiculum, subiculum, and tail) in n=1,398. We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium to assess groups with current PTSD, lifetime PTSD, and current PTSD in participants exposed to childhood trauma. We found that hippocampus and amygdala were smaller in subjects with current PTSD compared to trauma-exposed controls (hippocampus, Cohen’s D=-0.17, p=0.00054; amygdala, D=-0.11, p=0.025). Even though the female-only analysis contained approximately 1,100 fewer subjects than the full sample, the hippocampal results were more significant in females (p=0.00012), and Cohen’s D estimates indicated a stronger effect than in the full sample (D=-0.31 vs. D=-0.17). Current PTSD was associated with smaller subfield volume in the right hippocampal tail (p=0.002, D=0.26) and larger volumes in the right CA1 (p=0.002, D=0.26) in individuals exposed to at least one traumatic event in childhood. Our study is not subject to the biases of meta-analyses of published data, and represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma. The association of PTSD and abnormalities in the CA1 are consistent with its role in contextual fear memory, which is a widely accepted behavioral model for PTSD. The hippocampus and amygdala are crucial for fear processing, episodic and contextual learning and memory, processes related to PTSD symptomatology. This meta-analysis firmly establishes the importance of the hippocampus and amygdala in PTSD, which by itself represents a substantial step forward in identifying the most plausible neuroimaging phenotypes for a GWAS of PTSD.

DNA methylation levels are associated with CRF1 receptor antagonist treatment outcome in women with post-traumatic stress disorder

BackgroundWe have previously evaluated the efficacy of the CRF1 receptor antagonist GSK561679 in female PTSD patients. While GSK561679 was not superior to placebo overall, it was associated with a significantly stronger symptom reduction in a subset of patients with probable CRF system hyperactivity, i.e., patients with child abuse and CRHR1 SNP rs110402 GG carriers. Here, we test whether blood-based DNA methylation levels within CRHR1 and other PTSD-relevant genes would be associated with treatment outcome, either overall or in the high CRF activity subgroup.ResultsTherefore, we measured CRHR1 genotypes as well as baseline and post-treatment DNA methylation from the peripheral blood in the same cohort of PTSD-diagnosed women treated with GSK561679 (N = 43) or placebo (N = 45). In the same patients, we assessed DNA methylation at the PTSD-relevant genes NR3C1 and FKBP5, shown to predict or associate with PTSD treatment outcome after psychotherapy. We observed significant differences in CRHR1 methylation after GSK561679 treatment in the subgroup of patients with high CRF activity. Furthermore, NR3C1 baseline methylation significantly interacted with child abuse to predict PTSD symptom change following GSK561679 treatment.ConclusionsOur results support a possible role of CRHR1 methylation levels as an epigenetic marker to track response to CRF1 antagonist treatment in biologically relevant subgroups. Moreover, pre-treatment NR3C1 methylation levels may serve as a potential marker to predict PTSD treatment outcome, independent of the type of therapy. However, to establish clinical relevance of these markers, our findings require replication and validation in larger studies.Trial registrationNCT01018992. Registered 6 November 2009.

Cognitive Behavioral Therapy versus Eye Movement Desensitization and Reprocessing in Patients with Post-traumatic Stress Disorder: Systematic Review and Meta-analysis of Randomized Clinical Trials.

BackgroundPost-traumatic stress disorder (PTSD) is prevalent in children, adolescents and adults. It can occur alone or in comorbidity with other disorders. A broad range of psychotherapies such as cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) have been developed for the treatment of PTSD.AimThrough quantitative meta-analysis, we aimed to compare the efficacy of CBT and EMDR: (i) relieving the post-traumatic symptoms, and (ii) alleviating anxiety and depression, in patients with PTSD.MethodsWe systematically searched EMBASE, Medline and Cochrane central register of controlled trials (CENTRAL) for articles published between 1999 and December 2017. Randomized clinical trials (RCTs) that compare CBT and EMDR in PTSD patients were included for quantitative meta-analysis using RevMan Version 5.ResultsFourteen studies out of 714 were finally eligible. Meta-analysis of 11 studies (n = 547) showed that EMDR is better than CBT in reducing post-traumatic symptoms [SDM (95% CI) = -0.43 (-0.73 – -0.12), p = 0.006]. However, meta-analysis of four studies (n = 186) at three-month follow-up revealed no statistically significant difference [SDM (95% CI) = -0.21 (-0.50 – 0.08), p = 0.15]. The EMDR was also better than CBT in reducing anxiety [SDM (95% CI) = -0.71 (-1.21 – -0.21), p = 0.005]. Unfortunately, there was no difference between CBT and EMDR in reducing depression [SDM (95% CI) = -0.21 (-0.44 – 0.02), p = 0.08].ConclusionThe results of this meta-analysis suggested that EMDR is better than CBT in reducing post-traumatic symptoms and anxiety. However, there was no difference reported in reducing depression. Large population randomized trials with longer follow-up are recommended to build conclusive evidence.

Pre-traumatic vs post-traumatic OCD in PTSD patients: Are differences in comorbidity rates and functional health status related to childhood abuse?

ObjectiveThe goal of this study was to compare the clinical and functional status and the trauma-related characteristics of PTSD patients with comorbid OCD whose onset predated the index traumatic event (pre-traumatic OCD) with those of PTSD patient whose comorbid OCD only emerged after the exposure to the traumatic event (post-traumatic OCD). MethodsSixty-three individuals with PTSD and comorbid OCD were evaluated with the Structured Clinical Interview for DSM-IV AXIS I Disorders and completed the Posttraumatic Stress Disorder Checklist – Civilian Version, the Beck Depression Inventory, the Beck Anxiety Inventory, the Trauma History Questionnaire and the 36-Item Short-Form Health Survey. ResultsA history of childhood abuse was significantly more frequent among PTSD patients with pre-traumatic OCD (45.2%) than among their counterparts with post-traumatic OCD (16%). PTSD patients with pre-traumatic OCD had higher rates of psychiatric comorbidity in general and showed a lower functional health status in a physical domain (SF-36 Role Limitation due to Physical Health). In contrast, PTSD patients with post-traumatic OCD had a decreased functional health status in a psychological domain (SF-36 Emotional Well Being). The effect sizes were in the medium to large range. ConclusionsA history of child abuse may be an important, but often neglected, factor accounting for clinical, functional, and trauma-related differences between pre-traumatic and posttraumatic OCD in PTSD patients.

Molecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets.

The neurobiology of fear memory and extinction has been the subject of extensive research efforts that have increased our understanding of the brain regions, circuitry, and the cellular and molecular determinants of fear memory processes. However, the inability to access and directly study the brains of PTSD patients has made it difficult to translate the rodent fear memory studies to understand the neurobiological underpinnings of PTSD. The formation of a PTSD brain repository has recently been undertaken to address this issue. This will allow for high throughput gene expression and proteome analysis that can be coupled with epigenetic and genomic approaches to characterize the molecular alterations underlying PTSD. Preliminary studies using next generation RNA sequencing have identified PTSD specific gene expression alterations in the prefrontal cortex (PFC). The approaches used for transcriptome analysis and early findings regarding two glucocorticoid regulated genes of interest, FKBP5 and SGK1 are discussed, and the consequences of altered SGK1 are presented. Altered SGK1 could contribute to synaptic alterations in PFC subregions that could contribute to loss of inhibitory control and extinction of fear memories. Based on these findings, we discuss new studies demonstrating that ketamine can increase synapse number in the PFC and enhance the extinction of fear memory in rodent models and improve symptoms in PTSD patients. Continued molecular and cellular characterization of postmortem brain tissue of PTSD subjects will further define the neurobiology of PTSD and identify novel targets for safe and more efficacious treatments.

Reduced local segregation of single-subject gray matter networks in adult PTSD.

To psychoradiologically investigate the topological organization of single-subject gray matter networks in patients with PTSD. Eighty-nine adult PTSD patients and 88 trauma-exposed controls (TEC) underwent a structural T1 magnetic resonance imaging scan. The single-subject brain structural networks were constructed based on gray matter similarity of 90 brain regions. The area under the curve (AUC) of each network metric was calculated and both global and nodal network properties were measured in graph theory analysis. We used nonparametric permutation tests to identify group differences in topological metrics. Relationships between brain network measures and clinical symptom severity were analyzed in the PTSD group. Compared with TEC, brain networks of PTSD patients were characterized by decreased clustering coefficient (Cp ) (p = .04) and local efficiency (Eloc ) (p = .04). Locally, patients with PTSD exhibited altered nodal centrality involving medial superior frontal (mSFG), inferior orbital frontal (iOFG), superior parietal (SPG), middle frontal (MFG), angular, and para-hippocampal gyri (p < .05, corrected). A negative correlation between the segregation (Cp ) of gray matter and functional networks was found in PTSD patients but not the TEC group. Analyses of topological brain gray matter networks indicate a more randomly organized brain network in PTSD. The reduced segregation in gray matter networks and its negative relation with increased segregation in the functional network indicate an inverse relation between gray matter and functional changes. The present psychoradiological findings may reflect a compensatory increase in functional network segregation following a loss of segregation in gray matter networks.