Subjective sleep parameters: A marker to PTSD symptoms evolution? A 4-year longitudinal study.

Disturbed sleep is a common feature after exposure to a traumatic event, especially when PTSD develops. However, although there is evidence suggesting a potential role of sleep disturbance in the progression of PTSD symptoms, the interrelationship between sleep and PTSD symptoms has yet to be determined. In order to address this knowledge gap, we have investigated the influence of initial sleep characteristics on the evolution of post-traumatic stress disorder (PTSD) symptoms over 4 years of follow-up among individuals exposed to the Brazilian Kiss nightclub fire. Participants were individuals exposed to the 2013 Kiss nightclub fire in Brazil. Sleep characteristics and PTSD symptoms were measured within the 4 years following the fire by self-report questionnaires, such as The Pittsburgh Sleep Quality Index (PSQI), and PTSD Checklist - Civilian version (PCL-C). Generalized estimating equations (GEE) models were used to examine the longitudinal associations (by estimating the relative effects of initial sleep problems on PTSD symptoms after adjusting for covariates). Comprehensive information concerning socio-demographic factors, health status, and sleep complaints were obtained. A total of 232 individuals were included. In GEE models, no significant interactions were observed between sociodemographic variables and PTSD symptoms in the follow-up period, however, associations were found between PTSD at baseline and the following factors: the female gender, the victim individuals and the existence of prior psychiatric disease. Initial subjective sleep parameters were strongly associated with PTSD symptoms over 4 years, mainly the presence of disturbed dreams (p = 0.012), increased sleep latency (p = 0.029), and reduced sleep duration (p = 0.012). Sleep complaints and PTSD symptoms were common among individuals after the disaster. The current study has found that the presence of sleep complaints, especially increased sleep latency, presence of disturbed dreams and short sleep duration, in the initial presentation after the fire was consistently associated with the perpetration of PTSD symptoms in the next 4 years of follow-up. These findings suggest that interventions addressing these sleep complaints have the potential to reduce the persistence and/or severity of PTSD symptoms.

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD.

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

Post-traumatic stress disorder increases pain sensitivity by reducing descending noradrenergic and serotoninergic modulation.

Exposure to stress might influence pain sensitivity; however, little is known about whether post-traumatic stress disorder (PTSD)-like symptoms alter pain sensitivity and how it can happen. Male rats were exposed to the inescapable footshock paired with either social isolation or a control condition (not exposed to footshock but subjected to social isolation). After 7, 14, or 21 days, memory retention was evaluated. In the following three days, animals underwent the following tests: open-field, social interaction and formalin tests. Another group of animals were subjected to the object recognition test and to von Frey filaments. In other cohorts of animals, saline, fluoxetine, or desipramine were injected intrathecally and immunohistochemistry was performed to investigate whether PTSD-like symptoms alter the expression of c-Fos in serotonergic and noradrenergic neurons. Inescapable footshock induced the development of PTSD-like symptoms. Animals with PTSD-like symptoms showed an increase in the number of flinches in the formalin test and a reduction in mechanical threshold in the von Frey test at both retention intervals. The social interaction was negatively correlated with the nociceptive response in the formalin test. Fluoxetine or desipramine prevented the nociceptive response to chemical stimulus in the formalin test. In addition, in animals with PTSD-like symptoms, there was a reduction in c-Fos expression in serotonergic and noradrenergic neurons. Our results are important for the association of increased sensitivity to pain as one of the clinical manifestations that are present in the development of PTSD, and a possible treatment for increased pain sensitivity in male individuals with PTSD.

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review.

Lower sepsis mortality rates imply that more patients are discharged from the hospital, but sepsis survivors often experience sequelae, such as functional disability, cognitive impairment, and psychiatric morbidity. Nevertheless, the mechanisms underlying these long-term disabilities are not fully understood. Considering the extensive use of animal models in the study of the pathogenesis of neuropsychiatric disorders, it seems adopting this approach to improve our knowledge of postseptic psychiatric symptoms is a logical approach. With the purpose of gathering and summarizing the main findings of studies using animal models of sepsis-induced psychiatric symptoms, we performed a systematic review of the literature on this topic. Thus, 140 references were reviewed, and most of the published studies suggested a time-dependent recovery from behavior alterations, despite the fact that some molecular alterations persist in the brain. This review reveals that animal models can be used to understand the mechanisms that underlie anxiety and depression in animals recovering from sepsis.

Hidden wounds of violence: Abnormal motor oscillatory brain activity is related to posttraumatic stress symptoms.

Victims of urban violence are at risk of developing Posttraumatic Stress Disorder (PTSD), one of the most debilitating consequences of violence. Considering that PTSD may be associated with inefficient selection of defensive responses, it is important to understand the relation between motor processing and PTSD. The present study aims to investigate the extent to which the severity of posttraumatic stress symptoms (PTSS) is related to motor preparation against visual threat cues in victims of urban violence. Participants performed a choice reaction time task while ignoring a picture that could be threating or neutral. The EEG indices extracted were the motor-related amplitude asymmetry (MRAA) in the alpha frequency range, and the lateralized readiness potential (LRP). We observed a linear relation between longer LRP latency and a slower reaction time, selectively during threat processing (compared to neutral) in low PTSS, but not in high PTSS participants. Alpha MRAA suppression and the PTSS were also linearly related: the smaller the alpha MRAA suppression in the threat condition relative to neutral, the greater the PTSS. These results provide evidence that threatening cues affect motor processing that is modulated by the severity of PTSS in victims of urban violence.

Propranolol failed to prevent severe stress-induced long-term behavioral changes in male rats.

Memories of adverse events can be maladaptive when they lead to exaggerated fear, as observed in post-traumatic stress disorder (PTSD). Fear conditioning and fear sensitization are learning processes thought to play a role in fear-related disorders, and only few animal studies have evaluated the relationship between the associative and non-associative fear memory components on the development and maintenance of PTSD-like behavioral changes. Here we assessed the effects of a single dose of propranolol (10 mg/kg) or saline after fear memory retrieval on the long-term behavioral responses induced by severe stress in male rats. Animals were submitted to contextual fear conditioning (delayed shock group) or not (non-shock group) and underwent fear memory retrieval followed by propranolol or saline administration two weeks later. Rats were then evaluated in different behavioral tests to assess the expression of the conditioned fear response, anxiety-like and exploratory behaviors, and fear response after the presentation of unknown acoustic stimulus. Post-retrieval propranolol did not disrupt the subsequent expression of neither conditioned fear response nor the exploratory deficit and fear sensitization response, indicating that propranolol failed to mitigate long-term behavioral changes induced by severe stress in rats.

Neurocognitive reorganization of emotional processing following a socio-cognitive intervention in Colombian ex-combatants.

Ex-combatants often exhibit atypical Emotional Processing (EP) such as reduced emphatic levels and higher aggressive attitudes. Social Cognitive Training (SCT) addressing socio-emotional components powerfully improve social interaction among Colombian ex-combatants. However, with narrow neural evidence, this study offers a new testimony. A sample of 28 ex-combatants from Colombian illegal armed groups took part in this study, split into 15 for SCT and 13 for the conventional program offered by the Governmental Reintegration Route. All of them were assessed before and after the intervention with a protocol that included an EP task synchronized with electroencephalographic recordings. We drew behavioral scores and brain connectivity (Coherency) metrics from task performance. Behavioral scores yielded no significant effects. Increased post-intervention connectivity in the delta band was observed during negative emotional processing only SCT group. Positive emotions exposed distinctive gamma band connectivity that differentiate groups. These results suggest that SCT can trigger covert neurofunctional reorganization in ex-combatants embarked on the reintegration process even when overt behavioral improvements are not yet apparent. Such covert functional changes may be the neural signature of compensatory mechanisms necessary to reshape behaviors adaptively. This novel framework may inspire cutting-edge translational research at the crossing of neuroscience, sociology, and public policy-making.

Metabolic syndrome accentuates post-traumatic stress disorder-like symptoms and glial activation.

The relationship between individuals with post-traumatic stress disorder (PTSD) and the development of metabolic syndrome (MS) is well understood, but the relationship between individuals with preexisting MS and the development of PTSD is not yet known. Therefore, we evaluated the course of PTSD development in preexisting MS rats and we quantified the glial fibrillary acidic protein (GFAP) and ionized the calcium binding adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental animals. Male Wistar rats were divided into two groups: control or 10 % fructose for 5 weeks. After 5 weeks of MS induction, a group of animals was used to characterize MS. In another group, after 5 weeks of MS induction, animals were exposed to or not exposed to inescapable footshocks, followed by social isolation. After 14 days of a retention interval, the animals were re-exposed to the inescapable footshocks box, and the freezing time was evaluated. Over the following days, the animals were tested using the open field, social interaction and forced swimming tests, respectively. In another group of animals, after induction of MS and PTSD as previously described, elevated plus maze and object recognition tests were performed. Our results demonstrate that fructose solution for 5 weeks was able to induce MS, and animals with MS had more pronounced PTSD-like symptoms and a greater increase in GFAP and Iba-1 in the hippocampus and prefrontal cortex. In conclusion, MS accentuated PTSD-like symptoms that may be related to increased glial activation. This study helps reveal factors that may predispose individuals to the development of PTSD, such as metabolic disorders.

Case report on the multiple pathways to posttraumatic stress disorder following suicide.

Trauma pathology is not only a sum of risk factors, but emerges as a result of complex causal interaction. The case presented here illustrates the pathway from suicide exposure to the development of fully-fledged treatment-resistant posttraumatic stress disorder (PTSD), demonstrating how recognized risk factors can act in tandem to generate a difficult to treat syndrome. From a clinical perspective, bottom-up approaches that take into account real coping experiences of people bereaved by suicide are more effective to facilitate recovery and prevent adverse outcomes. Finally, even though treatment is often implemented, the diagnosis can be missed further complicating coping and treatment.

Pre- and postnatal alcohol exposure delays, in female but not in male rats, the extinction of an auditory fear conditioned memory and increases alcohol consumption.

Repeated exposure to alcohol increases retrieval of fear-conditioned memories, which facilitates, among other factors, the emergence of post-traumatic stress disorder (PTSD). Individuals with PTSD are more likely to develop alcohol and substance abuse related disorders. We assessed if prenatal and early postnatal alcohol exposure (PAE) increased the susceptibility to retain aversive memories and if this was associated with subsequent heightened alcohol consumption. Pregnant Sprague-Dawley rats were exposed for 22 hr/day, throughout pregnancy and until postnatal Day 7 to a single bottle of sucralose - sweetened 10% alcohol solution (PAE Group), or to a single bottle of tap water and sucralose (Control Group). Auditory fear conditioning (AFC) was performed in the adolescent offspring at postnatal Day 40. Freezing was measured during acquisition, retention and extinction phases, followed by 3 weeks of free choice alcohol intake. Female, but not male, PAE rats exhibited impaired extinction of the aversive memory, a finding associated with higher levels of 3-4 Dihidroxyphenylacetic acid (DOPAC) in the nucleus accumbens and heightened alcohol intake, respect to controls. These findings suggest that PAE makes females more vulnerable to long-term retention of aversive memories, which coexist with heightened alcohol intake. These findings are reminiscent of those of PTSD.

Increases in dendritic spine density in BLA without metabolic changes in a rodent model of PTSD.

Imaging studies have shown abnormal amygdala function in patients with posttraumatic stress disorder (PTSD). In addition, alterations in synaptic plasticity have been associated with psychiatric disorders and previous reports have indicated alterations in the amygdala morphology, especially in basolateral (BLA) neurons, are associated with stress-related disorders. Since, some individuals exposed to a traumatic event develop PTSD, the goals of this study were to evaluate the early effects of PTSD on amygdala glucose metabolism and analyze the possible BLA dendritic spine plasticity in animals with different levels of behavioral response. We employed the inescapable footshock protocol as an experimental model of PTSD and the animals were classified according to the duration of their freezing behavior into distinct groups: "extreme behavioral response" (EBR) and "minimal behavioral response". We evaluated the amygdala glucose metabolism at baseline (before the stress protocol) and immediately after the situational reminder using the microPET and the radiopharmaceutical 18F-FDG. The BLA dendritic spines were analyzed according to their number, density, shape and morphometric parameters. Our results show the EBR animals exhibited longer freezing behavior and increased proximal dendritic spines density in the BLA neurons. Neither the amygdaloid glucose metabolism, the types of dendritic spines nor their morphometric parameters showed statistically significant differences. The extreme behavior response induced by this PTSD protocol produces an early increase in BLA spine density, which is unassociated with either additional changes in the shape of spines or metabolic changes in the whole amygdala of Wistar rats.

Variability in response to severe stress: highly reactive rats exhibit changes in fear and anxiety-like behavior related to distinct neuronal co-activation patterns.

There is an important individual variability in development of posttraumatic stress disorder (PTSD) and this feature needs to be better addressed in preclinical studies. Previously we showed that only rats that explored the context before a foot shock (delayed shock group) exhibited long-lasting behavioral changes. In this study the delayed shock group was segregated using the freezing response upon re-exposure to the shock-paired context and we investigated whether higher reactivity would be related to behavioral alterations and to activation of brain regions using Fos immunoreactivity. The latter allowed the analysis of co-activity patterns among brain regions within each group, by creating connectivity maps. High responder rats (HR) displayed heightened freezing response upon context re-exposure, anxiety-like behavior, impaired exploratory behavior and fear sensitization. Fos analysis showed that HR displayed a negative correlation between the medial prefrontal cortex and the ventral hippocampus (vHPC) after the first context re-exposure. After the second context re-exposure, HR displayed reduced Fos expression in vHPC CA1 area, whereas low responders (LR) showed increased Fos in the paraventricular nucleus of the thalamus. Pearson correlation analyses revealed positive associations between freezing and Fos in the dorsal the periaqueductal gray and vHPC after exposure to unfamiliar acoustic stimulus in a novel environment. Thus, assessment of individual variability allowed the identification of a subset of reactive animals that displayed behavioral modifications relevant to PTSD. Fos correlation and network analyses revealed co-activity patterns in HR rats that may point out to associations of brain areas relevant to the behavioral outcomes.

Respiratory Health and Lung Function in Children Exposed to the World Trade Center Disaster.

OBJECTIVES: To compare lung function in a representative sample of World Trade Center (WTC)-exposed children with matched comparisons, and examine relationships with reported exposures. STUDY DESIGN: Study population consisted of 402 participants. Oscillometry, spirometry, and plethysmography were performed on WTC Health Registry (WTCHR) respondents who were ≤8 years of age on September 11, 2001 (n = 180) and a sociodemographically matched group of New York City residents (n = 222). We compared lung function by study arm (WTCHR and comparison group) as well as dust cloud (acute); home dust (subchronic); and other traumatic, nondust exposures. RESULTS: In multivariable models, post-9/11 risk of incident asthma was higher in the WTCHR participants than in the comparison group (OR 1.109, 95% CI 1.021, 1.206; P = .015). Comparing by exposure rather than by group, dust cloud (OR 1.223, 95% CI 1.095, 1.365; P < .001) and home dust (OR 1.123, 95% CI 1.029, 1.226; P = .009) exposures were also associated with a greater risk of incidence of post-9/11 asthma. No differences were identified for lung function measures. CONCLUSIONS: Although we cannot exclude an alternative explanation to the null findings, these results may provide some measure of reassurance to exposed children and their families regarding long-term consequences. Further study with bronchodilation and/or methacholine challenge may be needed to identify and further evaluate effects of WTC exposure. Biomarker studies may also be more informative in delineating exposure-outcome relationships. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02068183.

Peritraumatic tonic immobility is associated with PTSD symptom severity in Brazilian police officers: a prospective study.

OBJECTIVE: Peritraumatic reactions feature prominently among the main predictors for development of posttraumatic stress disorder (PTSD). Peritraumatic tonic immobility (PTI), a less investigated but equally important type of peritraumatic response, has been recently attracting the attention of researchers and clinicians for its close association with traumatic reactions and PTSD. Our objective was to investigate the role of PTI, peritraumatic panic, and dissociation as predictors of PTSD symptoms in a cohort of police recruits (n=132). METHODS: Participants were asked to complete the following questionnaires during academy training and after the first year of work: Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C), Physical Reactions Subscale (PRS), Peritraumatic Dissociative Experiences Questionnaire (PDEQ), Tonic Immobility Scale (TIS), and Critical Incident History Questionnaire. RESULTS: Employing a zero-inflated negative binomial regression model, we found that each additional point in the TIS was associated with a 9% increment in PCL-C mean scores (RM = 1.09), whereas for PRS, the increment was 7% (RM = 1.07). As the severity of peritraumatic dissociation increased one point in the PDEQ, the chance of having at least one symptom in the PCL-C increased 22% (OR = 1.22). CONCLUSIONS: Our findings highlight the need to expand investigation on the incidence and impact of PTI on the mental health of police officers.

Brain-derived neurotrophic factor and inflammatory markers in school-aged children with early trauma.

OBJECTIVE: The impact of childhood trauma (CT) on brain-derived neurotrophic factor (BDNF) and cytokines levels remains unclear. We investigated the association between CT and changes in BDNF and cytokines plasma levels in children. METHOD: We recruited 36 children with trauma (CT+) and 26 children without trauma (CT-). The presence of CT was based on a clinical interview and by Criteria A of DSM-IV criteria for PTSD. Blood samples were drawn from all children to assess BDNF and cytokines. ancova was performed with psychiatric symptoms and BMI as covariates to evaluate group differences in plasma levels. RESULTS: CT+ showed increased levels of BDNF and TNF-α after excluding children with history of inflammatory disease (P<0.05) when compared with those CT-. IL-12p70, IL-6, IL-8, IL-10, and IL-1ß levels were not statistically different between groups. CONCLUSION: CT+ showed increased BDNF and proinflammatory cytokines levels. The increase in BDNF levels may be an attempt to neutralize the negative effects of CT, while an increase in TNF-a levels be associated with a proinflammatory state after CT. How these changes associated with trauma relate to other biological changes and illness trajectory later in life remain to be further studied.

Psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A)

Objective: Sleep disturbances play a fundamental role in the pathophysiology posttraumatic stress disorder (PTSD), and are not only a secondary feature. The aim of this study was to validate and assess the psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A-BR), a self-report instrument designed to assess the frequency of seven disruptive nocturnal behaviors, in a sample of participants with and without PTSD. Methods: PSQI-A was translated into Brazilian Portuguese and applied to a convenience sample of 190 volunteers, with and without PTSD, who had sought treatment for the consequences of a traumatic event. Results: The PSQI-A-BR displayed satisfactory internal consistency (Cronbach's coefficient of 0.83 between all items) and convergent validity with the Clinician Administered PTSD Scale (CAPS), even when excluding sleep-related items (r = 0.52). Test-retest yielded high agreement in the global PSQI-A-BR, with good stability over time (r = 0.88). A global PSQI-A-BR cutoff score of 7 yielded a sensitivity of 79%, specificity of 64%, and a global score of 7 yielded a positive predictive value of 93% for discriminating participants with PTSD from those without PTSD. Conclusion: The PSQI-A-BR is a valid instrument for PTSD assessment, applicable to both clinical and research settings. .

Psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A).

OBJECTIVE: Sleep disturbances play a fundamental role in the pathophysiology posttraumatic stress disorder (PTSD), and are not only a secondary feature. The aim of this study was to validate and assess the psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A-BR), a self-report instrument designed to assess the frequency of seven disruptive nocturnal behaviors, in a sample of participants with and without PTSD. METHODS: PSQI-A was translated into Brazilian Portuguese and applied to a convenience sample of 190 volunteers, with and without PTSD, who had sought treatment for the consequences of a traumatic event. RESULTS: The PSQI-A-BR displayed satisfactory internal consistency (Cronbach's coefficient of 0.83 between all items) and convergent validity with the Clinician Administered PTSD Scale (CAPS), even when excluding sleep-related items (r = 0.52). Test-retest yielded high agreement in the global PSQI-A-BR, with good stability over time (r = 0.88). A global PSQI-A-BR cutoff score of 7 yielded a sensitivity of 79%, specificity of 64%, and a global score of 7 yielded a positive predictive value of 93% for discriminating participants with PTSD from those without PTSD. CONCLUSION: The PSQI-A-BR is a valid instrument for PTSD assessment, applicable to both clinical and research settings.

Post-traumatic stress disorder, dissociation, and neuropsychological performance in Latina victims of childhood sexual abuse.

This study compared the memory, attention/concentration, and executive functioning of 12 women with histories of child sexual abuse with a control group of 12 women without childhood abuse. Participants completed a neuropsychological test battery and various instruments assessing post-traumatic stress disorder and dissociation. The child sexual abuse group had lower performance than the control group on long- and short-term visual and verbal memory and presented more limited performance on executive functioning tasks. Functioning in these areas showed a negative correlation with post-traumatic stress disorder and dissociative symptoms. These findings suggest that child sexual abuse is associated with memory and executive functioning deficits and supports the idea that people with trauma histories and increased post-traumatic stress disorder and dissociation symptoms may have alterations in neuropsychological functioning.

They know their trauma by heart: an assessment of psychophysiological failure to recover in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) develops following exposure to atraumatic event and is characterized by persistent intense reactivity to trauma related cues. Equally important, but less studied, is the failure to restore physiological homeostasis after these excessive reactions. This study investigates psychophysiological markers of sustained cardiac activity after exposure to reminders of traumatic event in PTSD patients. METHODS: Participants passively listened to neutral and personal traumatic event while electrocardiogram was continuously recorded. Heart rate (HR) and heart rate variability (HRV) were analyzed in 19 PTSD patients and 16 trauma-exposed controls. RESULTS: Both PTSD patients and trauma exposed controls exhibited a significant increase in HR to the exposure of their personal trauma. PTSD patients sustained the increase of HR while controls recovered to basal levels. In PTSD patients, sustained HR was positively associated with re-experiencing symptoms. The PTSD group also showed a reduced HRV (a measure of parasympathetic influence on the heart) during personal trauma exposure and lack of recovery. LIMITATIONS: The sample size was small and PTSD patients were under medication. CONCLUSIONS: Our findings provide an experimental account of the failure of PTSD patients to exhibit physiological recovery after exposure to trauma-related stimuli. PTSD patients exhibited a sustained tachycardia with attenuation of HRV that persisted even after cessation of the stressor. Re-experiencing symptoms facilitated engagement in the trauma cues, suggesting that, in their daily-life, patients most likely present repeated episodes of sustained over-reactivity, which may underpin the emotional dysregulation characteristic of PTSD.