The relationship between tonic immobility and the development, severity, and course of posttraumatic stress disorder: Systematic and meta-analytic literature review.

BACKGROUND: Tonic immobility (TI) is a reflexive, involuntary response that causes motor inhibition, vocal suppression, and analgesia. TI is elicited by extreme fear and perception of entrapment in a life-threatening situation. Research suggests that TI is a frequent peritraumatic response and may be related to subsequent posttraumatic stress disorder (PTSD). However, findings are mixed and, as of yet, no systematic or meta-analytic review examining associations between TI and PTSD has been published. OBJECTIVE: We systematically and meta-analytically reviewed the literature and investigated whether TI is associated with the development, severity, and course of PTSD. Additionally, we evaluated whether different types of traumatic events are differentially associated with TI, and whether TI severity differs according to sex. METHODS: A systematic literature search was conducted using Embase, PubMed, PsycINFO, and Scopus. Meta-analyses were performed on the included articles. RESULTS: We identified 27 eligible articles. We found a significant association between TI and PTSD symptom severity (r = 0.39, 95% CI: 0.34-0.44; p < .0001). TI was more severe among females (Cohen's d=0.37, 95% CI: 0.25-0.48; p < .0001) and was more often elicited in situations involving interpersonal violence. We found limited longitudinal data to perform a meta-analysis of the association between TI and the development and/or course of PTSD. However, the literature available seems to support the role of TI in both the development and course of PTSD. CONCLUSIONS: Peritraumatic TI is associated with PTSD symptom severity, occurs more often during interpersonal violence, and is more severe among females. More longitudinal research is needed to investigate the role of TI in psychopathology development and course.

Sleep characteristics and inflammatory markers in women with post-traumatic stress disorder.

INTRODUCTION: Sexual violence is one of the most severe traumatic events. It is associated with a higher risk for post-traumatic stress disorder (PTSD) development. Sleep disturbances such as insomnia are frequently reported by PTSD patients and play a key role in the development and course of the disorder. Sleep disturbances are associated with higher levels of pro-inflammatory cytokines emphasizing the importance of sleep studies in individuals with PTSD. OBJECTIVES: To investigate the association between subjective and objective sleep measurements and PTSD symptoms with inflammatory markers in women with PTSD following sexual assault. METHODS: In this longitudinal study fifty-seven women with PTSD were evaluated for sleep measurements and inflammatory markers. Participants completed the Clinician-Administered PTSD Scale, the Beck Depression Inventory, the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index. In addition, patients underwent full in-lab polysomnography and serum levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) measurement. All assessments were performed at baseline and after one year. Patients received pharmacological and/or psychological interventions between baseline and one-year follow-up. RESULTS: Despite improving PTSD symptoms severity and sleep quality (expressed in PSQI), we found an increase in the inflammatory markers IL-1ß, TNF-α, IL-6 and CRP after one year of follow-up. These findings suggest that neurobiological processes may advance independently of PTSD symptoms. We found a significant increase in the levels of IL-1ß and TNF-α associated with decreased slow-wave sleep (p = 0.019 and p = 0.018 respectively), IL-6 associated with arousal index (p = 0.024), and CRP associated with insomnia severity (p = 0.012), and sleep duration longer than 6 h per night (p < 0.001). CONCLUSIONS: Sleep impairments in PTSD may be associated with a gradual and persistent alteration in the immune system, resulting in a progressive inflammatory process. Our results suggest that sleep mechanisms are involved in this incident inflammatory process in young women with PTSD.

Increased immuno-inflammatory mediators in women with post-traumatic stress disorder after sexual assault: 1-Year follow-up.

BACKGROUND: Sexual violence is a traumatic event that can trigger post-traumatic stress disorder (PTSD) and generate biological responses to stress characterized by inhibiting the hypothalamic-pituitary axis (HPA), altering immune activity, and changing the structure and function of the brain. PTSD is associated with increased levels of inflammatory markers. This study aimed to measure differences in inflammatory markers and HPA hormone levels between women with PTSD due to sexual violence and controls at baseline and after 1-year follow-up. METHODS: Fifty-eight women with PTSD resulting from sexual assault occurring up to 6 months prior were compared to 41 female controls. The patients were followed for 1 year. At baseline (T1), we measured inflammatory biomarkers. We also applied the Mini International Neuropsychiatric Interview (MINI), the Clinician-Administered Post-Traumatic Stress Disorder Scale-5, the Beck Depression Inventory, the Beck Anxiety Inventory, and the Childhood Trauma Questionnaire. The patients were randomized to receive treatment with sertraline or interpersonal psychotherapy for 14 weeks (T2) and then continued the usual treatment if deemed necessary for 1 year. The same interviews and examinations were repeated after 1 year (T3). RESULTS: At baseline, the patients had significantly higher adrenocorticotropic hormone levels, compared to controls; however, there was no baseline difference in inflammatory markers or cortisol. After 1 year, there were significantly higher levels of interleukin-1ß (p < 0.0001), monocyte chemoattractant protein-1 (p < 0.0001), tumor necrosis factor-α (p < 0.0001), c-reactive protein (p < 0.0001), and cortisol (p = 0.046) in the patient group. In addition to PTSD, 56 patients presented with a major depressive episode at T1 (according to the MINI). At the end of 1 year, there was a significant improvement in depressive (p < 0.001), anxiety (p = 0.03), and PTSD symptoms (p < 0.001) regardless of the treatment received. DISCUSSION: The increase of the inflammatory markers after 1 year, even with symptomatic improvement, may indicate that PTSD following sexual violence is associated with high depressive symptoms. This association may have a different pattern of immunoendocrine alterations than PTSD only. Furthermore, these alterations may persist in the long term, even with the improvement of the symptoms, probably generating an immunological imprint that can lead to future clinical consequences. This study adds to the current knowledge of PTSD neurobiology and contributes to broadening approaches to this disorder.

Posttraumatic stress disorder (PTSD) and depression severity in sexually assaulted women: hypothalamic-pituitary-adrenal (HPA) axis alterations.

BACKGROUND: Sexual assault is implicated in several adverse psychological and physical health outcomes, including posttraumatic stress disorder (PTSD) and depression. Neurobiological research has shown variations related to the hypothalamic-pituitary-adrenal (HPA) axis, immune alterations, metabolic function, and brain circuitry. Although these mechanisms have been extensively studied, the results have demonstrated different outcomes in PTSD. METHODS: We compared the plasma adrenocorticotropin (ACTH) and salivary cortisol levels of fifty-eight women with PTSD developed after sexual assault to those of forty-four female controls with no history of trauma. We also evaluated the psychiatric diagnosis and symptom severity of PTSD and depression. The participants' clinical conditions were associated with their hormonal levels to assess whether symptom severity was related to hormonal imbalance. RESULTS: A large percentage of sexually assaulted women had PTSD and comorbid depression. The ACTH levels were higher in the PTSD group than the control group and increased as PTSD severity increased, considering depressive symptoms, measured by the Beck Depression Inventory (BDI) (p < 0.0001), as well as PTSD symptoms, measured by subscale D of the Clinician-Administered PTSD Scale (CAPS-5) (p = 0.045) and the CAPS-5 total scale (p = 0.026). Cortisol levels measured at 10 pm were higher for the PTSD group than the control group (p = 0.045, p = 0.037, respectively), and the cortisol awakening response showed elevated cortisol levels for the PTSD group. CONCLUSIONS: These results show a correlation between symptom severity and HPA axis imbalance in patients with PTSD. Elevated ACTH and an elevated cortisol response in patients with comorbid depressive symptoms were the opposite of the expected response for patients with PTSD only. This association leads to the hypothesis that the neurobiological alterations of PTSD are related to the type of symptoms presented and their severity. These manifestations likely influence the disease course, prognosis and response to treatment. These outcomes highlight the need to discuss particular neurobiological alterations in patients with PTSD developed after sexual assault, mainly those with severe depressive symptoms.

Posttraumatic Stress Disorder and Neuroprogression in Women Following Sexual Assault: Protocol for a Randomized Clinical Trial Evaluating Allostatic Load and Aging Process Acceleration.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and severe disorder related to traumatic events. Women are disproportionately affected by PTSD than men and are more at risk in the occurrence of sexual assault victimization. Estimates suggest that 50% of women develop PTSD following sexual assault and successful clinical management can be challenging. Growing evidence has implicated neural, immune, and endocrine alterations underpinning PTSD, but only few studies have assessed the evolution of acute PTSD in women. OBJECTIVE: This study aims to measure whether the onset of PTSD is associated with accelerated aging in women following sexual assault. We hypothesize that the increase of allostatic load caused by PTSD leads to neuroprogression. We will implement a randomized clinical trial to compare responses to treatment with either interpersonal psychotherapy adapted for PTSD (IPT-PTSD) or the selective serotonin reuptake inhibitor sertraline. METHODS: We will include women between 18 and 45 years of age, who experienced sexual assault from 1 to 6 months before the initial evaluation, and present with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnosis of PTSD. Baseline evaluation will comprise clinical and psychometric assessments, structural and functional magnetic resonance imaging, neuropsychological testing, polysomnography, evaluation of immune and endocrine parameters, and genetic analyses. Age-matched female healthy controls will be included and subjected to the same evaluation. Patients will be randomized for treatment in 1 of the 2 arms of the study for 14 weeks; follow-up will continue until 1 year after inclusion via treatment as usual. The researchers will collect clinical and laboratory data during periodic clinical assessments up to 1-year follow-up. RESULTS: Data collection started in early 2016 and will be completed by the end of the first semester of 2020. Analyses will be performed soon afterward, followed by the elaboration of several articles. Articles will be submitted in early 2021. This research project has obtained a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/12559-5). CONCLUSIONS: We expect to provide insight into the consequences of recent sexual assault exposure in women by investigating the degree of neuroprogression developing from an early stage of PTSD. We also expect to provide important evidence on the efficacy of a non-exposure psychotherapy (IPT-PTSD) to mitigate PTSD symptoms in recently sexually assaulted women. Further, we aim to obtain evidence on how treatment outcomes are associated with neuroprogression measures. TRIAL REGISTRATION: Brazilian Clinical Trials Registry RBR-3z474z; http://www.ensaiosclinicos.gov.br/rg/RBR-3z474z/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19162.