Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

Purpose of Review

Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.

Recent Findings

Here, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity.

Summary

Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.

     

Posttraumatic stress disorder (PTSD) symptoms mediate the relationship between substance misuse and violent offending among female prisoners

Purpose

Despite empirical evidence suggesting complex associations between psychological trauma, substance misuse, and violent offending, there is a dearth of research investigating these associations in the female prison population.

Methods

A cross-sectional, interview-format questionnaire study was undertaken with a sample of 89 female prisoners. History of traumatic events, DSM-5 PTSD, drug use, and offending behaviour were assessed.

Results

Traumatic experiences had occurred in 97.8 % of the sample, while 60.5 % met criteria for a PTSD diagnosis. The majority of the sample (70.8 %) reported using illicit drugs, and 59.6 % had committed at least one violent offence. History of drug use was significantly correlated with trauma, PTSD status, and violent offending. A mediation analysis identified an indirect effect of PTSD symptoms on the relationship between history of drug use and violent offending.

Conclusions

The result of our mediation analysis further highlights the importance of addressing PTSD symptoms and substance misuse, among female offenders, to help prevent violent offending.

     

Posttraumatic Stress Disorder Symptoms and Problematic Overeating Behaviors in Young Men and Women

Background

Posttraumatic stress disorder (PTSD) is a risk factor for obesity, but the range of behaviors that contribute to this association are not known.

Purpose

The purpose of this study was to examine associations between self-reported PTSD symptoms in 2007, with and without comorbid depression symptoms, and three problematic overeating behaviors in 2010, and to estimate the associations of PTSD-related overeating behaviors with obesity.

Methods

Cross-sectional and longitudinal analyses included 7438 male (n = 2478) and female (n = 4960) participants from the Growing Up Today Study (mean age 22–29 years in 2010). Three eating behavior outcomes were assessed: binge eating (eating a large amount of food in a short period of time with loss of control), top quartile of coping-motivated eating (from the Motivations to Eat scale), and top quartile of disinhibited eating (from the Three-Factor Eating Questionnaire).

Results

PTSD symptoms were associated with two- to threefold increases in binge eating and top-quartile coping-motivated eating; having ≥4 PTSD symptoms, relative to no PTSD symptoms, was associated with covariate-adjusted RRs of 2.7 (95% CI 2.1, 3.4) for binge eating, 2.1 (95% CI 1.9, 2.4) for the top quartile of coping-motivated eating, and 1.5 (95% CI 1.3, 1.7) for the top quartile of disinhibited eating. There was a trend toward PTSD symptoms in 2007 predicting new onset binge eating in 2010. Having depression symptoms comorbid with PTSD symptoms further increased risk of binge eating and coping-motivated eating. All eating behaviors were associated with obesity.

Conclusion

Clinicians treating patients with PTSD should know of potential comorbid problematic eating behaviors that may contribute to obesity.

     

Sleep Disturbance in Posttraumatic Stress Disorder: Epiphenomenon or Causal Factor?

Purpose of Review

The goal of this review is to integrate recent findings on sleep disturbance and PTSD, examine sleep disturbance as a causal factor in the development of PTSD, and identify future directions for research, treatment, and prevention.

Recent Findings

Recent research highlights a relationship between both objective and subjective sleep disturbance and PTSD across diverse samples. Sleep disturbance also predicts PTSD over time. Finally, treatments targeting sleep disturbance lead to decreased PTSD symptoms, while standard PTSD treatments conclude with residual sleep disturbance.

Summary

Sleep disturbance may be more than a mere epiphenomenon of PTSD. Future research examining the causal role of sleep disturbance in the development of PTSD, as well as the utility of targeting sleep disturbance in prevention and treatment, is necessary to fully understand the likely bidirectional relationship between sleep disturbance and PTSD.

     

Potentially traumatic events have negative and positive effects on loneliness,depending on PTSD-symptom levels: evidence from a population-based prospective comparative study

Purpose

Examine to what extent adults affected by recent potentially traumatic events (PTE) with different PTSD-symptom levels are more at risk for post-event loneliness than non-affected adults are in the same study period.

Methods

We extracted data from the Dutch longitudinal LISS panel to measure pre-event loneliness (2011) and post-event loneliness (2013 and 2014), pre-event mental health problems (2011), PTE and PTSD symptoms (2012). This panel is based on a traditional random sample drawn from the population register by Statistics Netherlands.

Results

Results of the multinomial logistic regression analyses showed that affected adults with high levels of PTSD symptoms were more at risk for high levels of post-event loneliness than affected adults with very low PTSD-symptom levels and non-affected adults, while controlling for pre-event loneliness, pre-event mental health problems and demographics. However, affected adults with very low levels of PTSD symptoms compared to non-affected adults were less at risk for medium and high levels of post-event loneliness while controlling for the same variables. Yet, pre-event loneliness appeared to be the strongest independent predictor of loneliness at later stages: more than 80% with high pre-event levels had high post-event levels at both follow-ups.

Conclusions

Remarkably, potentially traumatic events have depending on PTSD-symptom levels both negative and positive effects on post-event loneliness in favor of affected adults with very low PTSD symptoms levels. However, post-event levels at later stages are predominantly determined by pre-event loneliness levels.

     

Dimensionality of <Emphasis Type="Italic">DSM-5</Emphasis> posttraumatic stress disorder and its association with suicide attempts: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III

Background

Emerging confirmatory factor analytic (CFA) studies suggest that posttraumatic stress disorder (PTSD) as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is best characterized by seven factors, including re-experiencing, avoidance, negative affect, anhedonia, externalizing behaviors, and anxious and dysphoric arousal. The seven factors, however, have been found to be highly correlated, suggesting that one general factor may exist to explain the overall correlations among symptoms.

Methods

Using data from the National Epidemiologic Survey on Alcohol and Related Conditions-III, a large, national survey of 36,309 U.S. adults ages 18 and older, this study proposed and tested an exploratory bifactor hybrid model for DSM-5 PTSD symptoms. The model posited one general and seven specific latent factors, whose associations with suicide attempts and mediating psychiatric disorders were used to validate the PTSD dimensionality.

Results

The exploratory bifactor hybrid model fitted the data extremely well, outperforming the 7-factor CFA hybrid model and other competing CFA models. The general factor was found to be the single dominant latent trait that explained most of the common variance (~76%) and showed significant, positive associations with suicide attempts and mediating psychiatric disorders, offering support to the concurrent validity of the PTSD construct.

Conclusions

The identification of the primary latent trait of PTSD confirms PTSD as an independent psychiatric disorder and helps define PTSD severity in clinical practice and for etiologic research. The accurate specification of PTSD factor structure has implications for treatment efforts and the prevention of suicidal behaviors.

     

The association of depression and posttraumatic stress disorder with the metabolic syndrome in a multi-ethnic cohort: the HELIUS study

Purpose

Depression and posttraumatic stress disorder (PTSD) may be linked to the metabolic syndrome (MetS). Consistency of this association across ethnic groups and the influence of comorbidity of depression/PTSD were examined.

Methods

Cross-sectional baseline data from the HELIUS study were used (4527 Dutch, 2999 South-Asian Surinamese, 4058 African Surinamese, 2251 Ghanaian, 3522 Turkish and 3825 Moroccan participants). The Patient Health Questionnaire-9 (PHQ-9) (score range 0–27) measured depressive symptoms. A 9-item questionnaire (score range 0–9) measured PTSD symptoms. The MetS was defined according to the International Diabetes Federation. The association of a depressed mood (PHQ-9 sum score?≥?10) and severe PTSD symptoms (sum score?≥?7) with the MetS was examined using logistic regression. Interaction with ethnicity and between a depressed mood and severe PTSD symptoms was tested.

Results

A depressed mood was associated with the MetS [OR (95% CI)?=?1.37 (1.24–1.51)] in the total sample and consistent across ethnic groups (p values for interaction all >?0.05). Severe PTSD symptoms were significantly associated with the MetS in the Dutch [OR (95% CI)?=?1.71 (1.07–2.73)]. The South-Asian Surinamese, Turks and Moroccans showed weaker associations than the Dutch (p values for interaction all <?0.05). A depressed mood and severe PTSD symptoms did not interact in the association with the MetS (p values for interaction?>?0.05).

Conclusions

A depressed mood was consistently associated with the MetS across ethnic groups, but the association between severe PTSD symptoms and the MetS maybe ethnicity dependent. The association with the MetS was not different in case of depressed mood/severe PTSD symptoms comorbidity.

     

Veterans are not the only ones suffering from posttraumatic stress symptoms: what do we know about dependents’ secondary traumatic stress?

Purpose

Previous research has mainly focused on veterans’ mental health problems, especially on posttraumatic stress disorder (PTSD). Less is known about the impact that the veteran’s experienced potentially traumatic events (PTEs) might have on their significant others. Therefore, we reviewed the scientific literature to find out what is known about the prevalence of secondary traumatic stress (STS) in significant others of veterans.

Methods

We systematically searched Pubmed, PsycINFO, Embase, Cochrane Library and PILOTS for relevant articles. This search resulted in 3100 records from which we included 48 articles.

Results

Two studies that reported on parental PTSD did not find evidence that parents were affected by their offspring’s experience. Nine studies that reported on PTSD in mainly adult children of veterans found only scant evidence that children were affected by their parent’s experienced PTE. Twenty-seven studies investigated PTSD symptoms in partners of veterans. Here results varied largely between studies with PTSD rates between 0 and 51 %.

Conclusions

Overall, we found the strongest evidence of STS in partners of help-seeking veterans with PTSD. The lack of clarity provided by the currently available evidence suggests a pressing need for further work to examine this subject in more detail.

     

Untangling PTSD and TBI: Challenges and Strategies in Clinical Care and Research

Purpose of Review

Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) can result from similar injuries and can result in similar symptoms, such as problems with sleep, concentration, memory, and mood. Although PTSD and persistent sequelae due to a TBI (PST) have generally been viewed as pragmatically confounded but conceptually separable entities, we examine emerging evidence emphasizing the breadth of overlap in both clinical presentation and underlying pathophysiology between PST and PTSD.

Recent Findings

New evidence underscores the poor specificity of symptoms to etiology and emphasizes the potential, after both physical brain injury and traumatic stress, for changes in each of the three interacting systems that coordinate the body’s response to the experience or expectation of major injury—the immune, endocrine, and neuromodulatory neurotransmitter systems.

Summary

A view of PTSD and PST sharing common pathophysiologic elements related to the CNS response to acute injury or threat carries important implications for research and clinical care.

     

Impact of Gender on Child and Adolescent PTSD

Purpose of Review

This review examines the recent literature on biological factors that influence sex differences in posttraumatic stress disorder (PTSD) during childhood and adolescence, focusing on neurobiological, hormonal, and genetic factors that may increase risk in girls.

Recent Findings

More than 60% of children and adolescents are exposed to traumatic events, and many develop PTSD. There is increasing recognition of gender differences in PTSD, with women having double the rates of the disorder compared to men. These gender differences in symptoms and their underlying neurobiology appear to emerge during adolescence, although it is still unclear which biological mechanisms may play key roles in the development of sex difference.

Summary

The literature on gender effects in children and adolescents is still in the early stages, and more prospective and longitudinal work is needed; however, estrogen appears to play a key role in increasing risk for PTSD in girls, which emerges in adolescence.

     

The Walking Wounded: Emerging Treatments for PTSD

Purpose of Review

We review the published literature over the last 24 months in the treatment of PTSD for our military men and women. We examined the updated clinical practice guidelines published in June 2017 by the Veteran’s administration and Department of Defense and contrasted the guidelines with the most recent literature. We also discuss new directions in PTSD research.

Recent Findings

Psychotherapy remains one of the most effective treatments for PTSD; unfortunately, few participants remain in treatment to completion. Many of the emerging therapies target NMDA receptor antagonists, cannabinoid receptor modulators, glucocorticoid receptor agonists, non-SSRI antidepressants, and opioid receptor agonists. The newer therapies fall into the drug classes of anti-hypertensives, glutamate modulators, oxytocin, and medication targeting insomnia/hyperarousal.

Summary

PTSD symptoms are often chronic in our veteran population. While current treatments are helpful, there are often significant residual symptoms. We reviewed the most recent improvements in treatment and discuss therapies that are in the research phase.

     

Network approach to the symptom-level association between alcohol use disorder and posttraumatic stress disorder

Purpose

The high prevalence of alcohol use disorder among individuals with a history of trauma and posttraumatic stress disorder is well documented. The current study applied network analysis to map the structure of symptom associations between these disorders.

Methods

Data come from a community sample of 449 Australian adults with a history of trauma and alcohol consumption during the last 12 months. Data analysis consisted of the construction of the comorbidity network of PTSD/AUD symptoms, identification of the bridging symptoms, computation of the centrality measures, and evaluation of the robustness of the results.

Results

Results highlighted two main symptom clusters, corresponding to two disorders, and that only nine edges connected the two clusters. Bridging symptoms connecting the two clusters were: alcohol use in dangerous situations, physical or mental health problems as a result of alcohol use, loss of interest or reduced social activities, and reckless/self-destructive behaviour.

Conclusions

Identification of both central symptoms, because of their key role in the constellation and strong associations with majority of symptoms, and bridge symptoms, because of their mediating role between two disorders, has some implications in terms of self-medication and risk-taking/self-regulation theories of comorbidity and provides a number of clinical implications, which warrants further exploration within clinical samples.

     

Posttraumatic stress disorder,trauma, and reconciliation in South Sudan

Purpose

South Sudan is embroiled in a conflict that erupted in December 2013. This study examines what people in South Sudan think is necessary to achieve reconciliation and how trauma exposure and PTSD are associated with those beliefs.

Methods

1525 participants (51.0% female) were selected using random and purposive sampling in six states and Abyei. Participants reported on traumatic events, PTSD symptoms, and attitudes towards reconciliation mechanisms.

Results

Results indicated that 40.7% met symptom criteria for probable PTSD. Most participants thought reconciliation was not possible without prosecuting perpetrators or compensating victims and did not support amnesty. Participants with probable PTSD were more likely to endorse confessions (OR 2.42 [1.75, 3.35]), apologies (OR 2.04 [1.46, 2.83]), and amnesty (OR 1.58 [1.21, 2.08]), and to report that compensation (OR 2.32 [1.80, 3.00]) and prosecution (OR 1.47 [1.15, 1.89]) were not necessary for reconciliation. The more traumatic events people experienced, the more they endorsed criminal punishment for perpetrators (OR 1.07 [1.04, 1.10]) and the less they endorsed confessions (OR 0.97 [0.95, 0.99]).

Conclusions

People with PTSD may prioritize ending violence via opportunities for reconciliation, while those with more trauma exposure may support more punitive mechanisms. Policy makers should take mental health treatment and trauma into account when designing conflict mitigation, peace building, and justice mechanisms.

     

Traumatic exposure,acculturative stress and cultural orientation: the influence on PTSD,depressive and anxiety symptoms among refugees

Objective

Acculturation studies conducted with refugees have predominantly concentrated on investigating the impact of acculturative stress on mental health, and have neglected to investigate the impact of cultural orientations towards the host and ethnic cultures. Furthermore, exposure to traumas is highly prevalent in refugees and strongly associated with mental health outcomes, however, rarely included in investigations of acculturative process of refugees.

Method

Using structural equation modelling, this study tested an integrated model of the relationship between traumatic exposure, acculturative stress, host and ethnic cultural orientations and posttraumatic stress disorder (PTSD), depression and anxiety symptoms among 138 Bosnian refugees resettled in Australia and Austria.

Results

The model showed an overall good fit and noteworthy amount of variance indicating that traumatic exposure is the strongest direct and indirect predictor of PTSD, depression and anxiety symptoms. Furthermore, acculturative stress was identified as a significant risk factor influencing host cultural orientation, mediating the effect of traumatic exposure on all mental health outcomes.

Conclusion

Acculturative stress and cultural and social stressors that are related to acculturation need to be addressed alongside provision of effective psychotherapy, especially since they are significant impediments to host cultural orientation and constructive engagement with mental health services in refugees.

     

Recent Advancements in Treating Sleep Disorders in Co-Occurring PTSD

Purpose of Review

Comorbidity of posttraumatic stress disorder (PTSD) and insomnia, nightmares, and obstructive sleep apnea (OSA) is high. We review recent research on psychotherapeutic and pharmacological interventions for sleep disorders in PTSD.

Recent Findings

PTSD treatments decrease PTSD severity and nightmare frequency, but do not resolve OSA or insomnia. Research on whether insomnia hinders PTSD treatment shows mixed results; untreated OSA does interfere with PTSD treatment. Cognitive behavioral therapy for insomnia is the recommended treatment for insomnia; however, optimal ordering with PTSD treatment is unclear. PTSD treatment may be most useful for PTSD-related nightmares. CPAP therapy is recommended for OSA but adherence can be low.

Summary

Targeted treatment of sleep disorders in the context of PTSD offers a unique and underutilized opportunity to advance clinical care and research. Research is needed to create screening protocols, determine optimal order of treatment, and elucidate mechanisms between sleep and PTSD treatments.

     

PTSD and Physical Health

Purpose of Review

We review evidence linking PTSD to physical health symptoms and specific disorders, highlighting areas with multiple studies and objective measures of disease states when available. We also examine evidence for biological, behavioral, and psychosocial mechanisms underlying these associations and discuss the clinical implications of recent research.

Recent Findings

Recent meta-analyses have found that evidence is particularly strong for increased risk of cardiovascular, metabolic, and musculoskeletal disorders among patients with PTSD. Numerous studies have found alterations in the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, inflammation, and health behaviors that could increase risk of illness, but few studies have simultaneously incorporated measures of mechanisms and disease outcomes.

Summary

Future research should focus on expanding the diversity of populations studied, particularly with respect to underrepresented racial and ethnic groups. Longitudinal studies that incorporate repeated measures of PTSD, pathogenic mechanisms of disease, and physical health outcomes and the addition of physical health outcomes to PTSD treatment trials will be most informative for the field.

     

Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related Abnormalities in Brain Structure,Amyloid, and Inflammation

Purpose of Review

Posttraumatic stress disorder (PTSD) is associated with increased risk for dementia, yet mechanisms are poorly understood.

Recent Findings

Recent literature suggests several potential mechanisms by which sleep impairments might contribute to the increased risk of dementia observed in PTSD. First, molecular, animal, and imaging studies indicate that sleep problems lead to cellular damage in brain structures crucial to learning and memory. Second, recent studies have shown that lack of sleep might precipitate the accumulation of harmful amyloid proteins. Finally, sleep and PTSD are associated with elevated inflammation, which, in turn, is associated with dementia, possibly via cytokine-mediated neural toxicity and reduced neurogenesis.

Summary

A better understanding of these mechanisms may yield novel treatment approaches to reduce neurodegeneration in PTSD. The authors emphasize the importance of including sleep data in studies of PTSD and cognition and identify next steps.

     

Trauma,PTSD, and the Developing Brain

Purpose of Review

PTSD in youth is common and debilitating. In contrast to adult PTSD, relatively little is known about the neurobiology of pediatric PTSD, nor how neurodevelopment may be altered. This review summarizes recent neuroimaging studies in pediatric PTSD and discusses implications for future study.

Recent Findings

Pediatric PTSD is characterized by abnormal structure and function in neural circuitry supporting threat processing and emotion regulation. Furthermore, cross-sectional studies suggest that youth with PTSD have abnormal frontolimbic development compared to typically developing youth. Examples include declining hippocampal volume, increasing amygdala reactivity, and declining amygdala-prefrontal coupling with age.

Summary

Pediatric PTSD is characterized by both overt and developmental abnormalities in frontolimbic circuitry. Notably, abnormal frontolimbic development may contribute to increasing threat reactivity and weaker emotion regulation as youth age. Longitudinal studies of pediatric PTSD are needed to characterize individual outcomes and determine whether current treatments are capable of restoring healthy neurodevelopment.

     

Sleep and Dreaming in Posttraumatic Stress Disorder

Purpose of Review

Sleep disturbances are core features of posttraumatic stress disorder (PTSD). This review aims to characterize sleep disturbances, summarize the knowledge regarding the relationships between trauma exposure and sleep difficulties, and highlight empirically supported and/or utilized treatments for trauma-related nightmares and insomnia.

Recent Findings

Trauma-related nightmares and insomnia, and other sleep disorders, are frequently reported among trauma survivors. The roles of fear of sleep, REM density, and decreased parasympathetic activity are beginning to inform the relationship between trauma exposure and sleep difficulties. Additionally, the potential adaptive role of sleep loss immediately following a traumatic experience is being recognized. Interventions targeting these sleep disturbances show promise in reducing symptoms.

Summary

Research in understanding the role of sleep on the development, course, and treatment of PTSD is expanding. Longitudinal investigations are needed to further elucidate these relationships and identify treatments most effective in ameliorating symptoms.