Pathophysiology Of Posttraumatic Stress Disorder Research Articles

Hypothalamus and Post-Traumatic Stress Disorder: A Review.

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual's ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic-pituitary-adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition.

PTSD, subsequent violence, and increased focus on trauma-informed care

PTSD, subsequent violence, and increased focus on trauma-informed care

Investigating TSPO levels in occupation-related posttraumatic stress disorder

Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5–30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic–pituitary–adrenal-axis dysregulation and central immune response to trauma which warrants further study.

Altered dynamic functional connectivity associates with post-traumatic stress disorder.

Research has been looking into neural pathophysiology of post-traumatic stress disorder (PTSD) and dynamic functioning connectivity (dFC) applying resting state functional magnetic resonance imaging (rs-fMRI). Previous studies showed that PTSD related impairments are associated with alterations distributed across different brain regions and disorganized functional connectivity, especially in Default Mode Network and the cerebellar area. In this study, we specifically looked into dFC on a whole brain level, and we focused on critical regions such as DMN and cerebellum. To explore the characteristics of dFC among patients with PTSD, we collected rs-fMRI data from 27 PTSD patients and 30 healthy controls. The study also added a control group of 33 trauma-exposed individuals to further look into trauma impact. Utilizing group spatial independent component analysis (ICA), the dynamic properties on whole brain level were detected with sliding time window approach, and k-means clustering. Two reoccurring FC "States" were identified, with connections being more concentrated on a within-network level in one state and more strongly inter-connected in the other state. Abnormalities in dFC were found within DMN, between DMN and cerebellum, and between DMN and visual network for PTSD patients. The findings were in accordance with the study hypothesis that the dFC alterations might point to deficits in emotional modulation and dysfunctional self-referential thought. Abnormalities in dFC among PTSD patients might also be indicators of PTSD symptoms including depression and anxiety, hypervigilance, impaired cognitive functioning and self-referential information processing.

Underlying Hippocampal Mechanism of Posttraumatic Stress Disorder Treatment Outcome: Evidence From Two Clinical Trials

BackgroundThe hippocampus plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD) and its prognosis. Accumulating findings suggest that individuals with larger pretreatment hippocampal volume are more likely to benefit from PTSD treatment, but the mechanism underlying this effect is unknown. We investigated whether further increase in hippocampal volume during treatment explains the better prognosis of individuals with greater pretreatment hippocampal volume. MethodsWe collected structural magnetic resonance imagesfrom patients with PTSD before and after treatment. We examined whether larger hippocampal volume moderates the effect of increased hippocampal volume during treatment on symptom reduction. Given the relatively small sample sizes of treatment studies with pre- and posttreatment magnetic resonance imaging, we focused on effect sizes and sought to replicate findings in an external sample. We tested our hypothesis in study 1 (N = 38; prolonged exposure therapy) and then tested whether the results could be externally replicated in study 2 (N = 20; ketamine infusion followed by exposure therapy). ResultsFindings from study 1 revealed that increased right hippocampal volume during treatment was associated with greater PTSD symptom reduction only in patients with greater pretreatment right hippocampal volume (p = .03; η2 = 0.13, a large effect). Findings were partially replicated in study 2 for depressive symptoms (p = .034; η2 = 0.25, a very large effect) and for PTSD symptoms (p = .15; η2 = 0.15, a large effect). ConclusionsElucidating increased hippocampal volume as one of the neural mechanisms predictive of therapeutic outcome for individuals with larger pretreatment hippocampal volume may help identify clinical targets for this subgroup.

Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats

Background Females are twice as likely to experience post-traumatic stress disorder (PTSD) than males, yet specific factors contributing to this greater risk are not fully understood. Our clinical and recent preclinical findings suggest a role for the metabotropic glutamate receptor 5 (mGlu5) in PTSD and differential involvement between males and females. Methods Here, we further investigate whether mGlu5 receptor availability may contribute to individual and sex differences in PTSD susceptibility by quantifying receptor availability using the mGlu5 receptor-specific radiotracer, [18F]FPEB, and positron emission tomography in male (n = 16) and female (n = 16) rats before and after traumatic footshock exposure (FE) and assessment of stress-enhanced fear learning (SEFL) susceptibility, as compared with no-shock controls (CON; n = 7 male; n = 8 female). Results Overall, FE rats displayed greater fear generalization as compared with CON (p < .001). Further, greater mGlu5 receptor availability at baseline (p = .003) and post-test (p = .005) was significantly associated with expression of the SEFL phenotype. Notably, FE female rats displayed a shift to more passive coping (ie, freezing), and displayed greater SEFL susceptibility (p = .01), and had lower baseline mGlu5 availability (p = .03) relative to their FE male rat counterparts. Conclusion Results are consistent with clinical findings of higher mGlu5 receptor availability in PTSD, and add to growing evidence implicating these receptors in the pathophysiology of PTSD and sex-differences in susceptibility for this disorder.

Fear Extinction Learning in Posttraumatic Stress Disorder.

Impairments in fear extinction processes have been implicated in the genesis and maintenance of debilitating psychopathologies, including Posttraumatic stress disorder(PTSD). PTSD, classified as a trauma- and stressor-related disorder, is characterized by four symptom clusters: intrusive recollections of trauma, avoidance of trauma-related stimuli, alterations in cognition and mood, and hyperarousal. One of the key pathological feature associated with the persistence of these symptoms is impaired fear extinction, as delineated in multiple studies employing Pavlovian fear-conditioning paradigms. These paradigms, comprising fear acquisition, extinction, extinction recall, and fear renewal phases, have illuminated the neurobiological substrates of PTSD. Dysfunctions in the neural circuits that mediate these fear learning and extinction processes can result in failure to extinguish fear responses and retain extinction memory, giving rise to enduring experience of fear and anxiety. The protective avoidance behaviors observed in individuals with PTSD further exacerbate intrusive symptoms and pose challenges to effective treatment strategies. A comprehensive analysis of fear conditioning and extinction processes, along with the underlying neurobiology, could significantly enhance our understanding of PTSD pathophysiology. This chapter delineates the role of fear extinction processes in PTSD, investigates the underlying neurobiological substrates, and underscores the therapeutic implications, while also identifying future research directions.

Towards assessing subcortical "deep brain" biomarkers of PTSD with functional near-infrared spectroscopy.

Assessment of brain function with functional near-infrared spectroscopy (fNIRS) is limited to the outer regions of the cortex. Previously, we demonstrated the feasibility of inferring activity in subcortical "deep brain" regions using cortical functional magnetic resonance imaging (fMRI) and fNIRS activity in healthy adults. Access to subcortical regions subserving emotion and arousal using affordable and portable fNIRS is likely to be transformative for clinical diagnostic and treatment planning. Here, we validate the feasibility of inferring activity in subcortical regions that are central to the pathophysiology of posttraumatic stress disorder (PTSD; i.e. amygdala and hippocampus) using cortical fMRI and simulated fNIRS activity in a sample of adolescents diagnosed with PTSD (N = 20, mean age = 15.3 ± 1.9years) and age-matched healthy controls (N = 20, mean age = 14.5 ± 2.0years) as they performed a facial expression task. We tested different prediction models, including linear regression, a multilayer perceptron neural network, and a k-nearest neighbors model. Inference of subcortical fMRI activity with cortical fMRI showed high prediction performance for the amygdala (r >0.91) and hippocampus (r >0.95) in both groups. Using fNIRS simulated data, relatively high prediction performance for deep brain regions was maintained in healthy controls (r >0.79), as well as in youths with PTSD (r >0.75). The linear regression and neural network models provided the best predictions.

Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD.

Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS−) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.

Decoding Shared Versus Divergent Transcriptomic Signatures Across Cortico-Amygdala Circuitry in PTSD and Depressive Disorders.

Posttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease that is highly comorbid with major depressive disorder (MDD) and bipolar disorder. The overlap in symptoms is hypothesized to stem from partially shared genetics and underlying neurobiological mechanisms. To delineate conservation between transcriptional patterns across PTSD and MDD, the authors examined gene expression in the human cortex and amygdala in these disorders. RNA sequencing was performed in the postmortem brain of two prefrontal cortex regions and two amygdala regions from donors diagnosed with PTSD (N=107) or MDD (N=109) as well as from neurotypical donors (N=109). The authors identified a limited number of differentially expressed genes (DEGs) specific to PTSD, with nearly all mapping to cortical versus amygdala regions. PTSD-specific DEGs were enriched in gene sets associated with downregulated immune-related pathways and microglia as well as with subpopulations of GABAergic inhibitory neurons. While a greater number of DEGs associated with MDD were identified, most overlapped with PTSD, and only a few were MDD specific. The authors used weighted gene coexpression network analysis as an orthogonal approach to confirm the observed cellular and molecular associations. These findings provide supporting evidence for involvement of decreased immune signaling and neuroinflammation in MDD and PTSD pathophysiology, and extend evidence that GABAergic neurons have functional significance in PTSD.

Post-traumatic stress disorder: a psychiatric disorder requiring urgent attention.

Post-traumatic stress disorder (PTSD) is a severe and heterogenous psychiatric disorder that was first defined as a mental disorder in 1980. Currently, the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and the International Classification of Diseases 11th Edition (ICD-11) offer the most widely accepted diagnostic guidelines for PTSD. In both diagnostic categories, experiencing a traumatic event (TE) is the necessary criterion for diagnosing PTSD. The TEs described in the DSM-5 include actual or threatened death, serious injury, sexual violence, and other extreme stressors, either directly or indirectly. More than 70% of adults worldwide are exposed to a TE at least once in their lifetime, and approximately 10% of individuals develop PTSD after experiencing a TE. The important features of PTSD are intrusion or re-experiencing fear memories, pervasive sense of threat, active avoidance, hyperarousal symptoms, and negative alterations of cognition and mood. Individuals with PTSD have high comorbidities with other psychiatric diseases, including major depressive disorder, generalized anxiety disorder, and substance use disorder. Multiple lines of evidence suggest that the pathophysiology of PTSD is complex, involving abnormal neural circuits, molecular mechanisms, and genetic mechanisms. A combination of both psychotherapy and pharmacotherapy is used to treat PTSD, but has limited efficacy in patients with refractory PTSD. Because of the high prevalence, heavy burden, and limited treatments, PTSD is a psychiatric disorder that requires urgent attention. In this review, we summarize and discuss the diagnosis, prevalence, TEs, pathophysiology, and treatments of PTSD and draw attention to its prevention.

Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model.

Accumulating evidence suggests that the activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome contributes to the pathophysiology of post-traumatic stress disorder (PTSD). Astrocytes, the homeostatic cells of the central nervous system are intimately involved into pathophysiology of various mental disorders including PTSD. We demonstrated previously that leptin exerts neuroprotection and ameliorates chronic sleep deprivation-induced depressive-like behaviours. Here, we extended the study of therapeutic effects of leptin to PTSD model mice. We discovered that PTSD is associated with significant activation of NLRP3 inflammasome in astrocytes sorted from GFAP-GFP transgenic mice, while administration of leptin markedly suppressed the activation of astrocytic NLRP3 inflammasome. Leptin effectively improved PTSD-associated behavioural alterations including fear memory, cognitive impairments, and depressive-like behaviours. Therapeutic effects of leptin were mediated by the signal transducer and activator of transcription 3 (STAT3) in astrocytes. In addition, the PTSD-related activation of NLRP3 inflammasome impairs astrocytic mitochondria suppressing ATP synthesis and leading to an increased ROS production. Leptin reversed mitochondrial inhibition by stimulating STAT3 in astrocytes. We propose leptin as a novel candidate for the pharmacological treatment of PTSD.

Morning light treatment for traumatic stress: The role of amygdala reactivity study protocol.

BackgroundExposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye.MethodsIn this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment.DiscussionMorning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

P614. The Role of NUDT6 and S100A9 as New Molecular Players in Hippocampus, Basolateral Amygdala and Prefrontal Cortex in a Post-Traumatic Stress Disorder (PTSD) Model

Hippocampal overexpression of NUDT6, a protein transcribed from the antisense strand of the FGF2 gene, increased anxiety-like behaviour along with S100A9 levels. Besides, it impaired spatial memory yet improved fear-related memory in rats. Since this behavioural phenotype has a strong resemblance with PTSD, we investigated whether NUDT6 and/or S100A9 play a role in the pathophysiology of PTSD.

P616. The VPAC2 Receptor Mediates Fear Learning in Female, but Not Male Mice

Pituitary adenylate cyclase activating peptide (PACAP) is a neuropeptide that has been previously implicated in the pathophysiology of post-traumatic stress disorder (PTSD). Although PACAP binds to the vasoactive intestinal peptide receptor 2 (VPAC2) it is still unknown whether VPAC2 mediates stress-induced psychiatric disease. Here, we evaluated whether pharmacological activation of VPAC2 via Bay 55-9837, a VPAC2-selective peptide agonist, could attenuate stress-induced behaviors in male and female mice.

Metabolomics analysis of post-traumatic stress disorder symptoms in World Trade Center responders

Metabolomics has yielded promising insights into the pathophysiology of post-traumatic stress disorder (PTSD). The current study expands understanding of the systems-level effects of metabolites by using global metabolomics and complex lipid profiling in plasma samples from 124 World Trade Center responders (56 PTSD, 68 control) on 1628 metabolites. Differential metabolomics analysis identified hexosylceramide HCER(26:1) associated with PTSD at FDR < 0.1. The multi-metabolite composite score achieved an AUC of 0.839 for PTSD versus unaffected control classification. Independent component analysis identified three metabolomic modules significantly associated with PTSD. These modules were significantly enriched in bile acid metabolism, fatty acid metabolism and pregnenolone steroids, which are involved in innate immunity, inflammatory process and neuronal excitability, respectively. Integrative analysis of metabolomics and our prior proteomics datasets on subsample of 96 responders identified seven proteomic modules significantly correlated with metabolic modules. Overall, our findings shed light on the molecular alterations and identify metabolomic-proteomic signatures associated with PTSD by using machine learning and network approaches to enhance understanding of the pathways implicated in PTSD. If present results are confirmed in follow-up studies, they may inform development of novel treatments.

Neuroinflammation in Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a well-known mental illness, which is caused by various stressors, including memories of past physical assaults and psychological pressure. It is diagnosed as a mental and behavioral disorder, but increasing evidence is linking it to the immune system and inflammatory response. Studies on the relationship between inflammation and PTSD revealed that patients with PTSD had increased levels of inflammatory cytokine biomarkers, such as interleukin-1, interleukin-6, tumor necrosis factor-α, nuclear factor-κB, and C-reactive protein, compared with healthy controls. In addition, animal model experiments imitating PTSD patients suggested the role of inflammation in the pathogenesis and pathophysiology of PTSD. In this review, we summarize the definition of PTSD and its association with increased inflammation, its mechanisms, and future predictable diseases and treatment possibilities. We also discuss anti-inflammatory treatments to address inflammation in PTSD.

Oxytocin receptor genes moderate BDNF epigenetic methylation by childhood trauma

ObjectivesGene-Environment (G × E) interaction is of increasing importance in understanding the pathophysiology of posttraumatic stress disorder (PTSD). This study investigated the interaction effect of childhood traumatic experience and epigenetic methylation of brain-derived neurotrophic factor (BDNF) and a possible moderating effect of oxytocin receptor (OXTR) gene rs53576. MethodsNinety-nine patients with PTSD and 81 healthy controls (HCs) were recruited. Clinical assessments, including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. BDNF methylation and OXTR genotyping (A vs. G allele) were conducted through blood sampling. A two-way multivariate analysis and a moderated regression analysis were conducted to investigate the moderating effect of the OXTR gene on the relationship between CTQ and BDNF methylation. ResultsAs for the HC group, the interaction effect of the CTQ and OXTR genotype was significant on BDNF methylation, and the moderation model showed that CTQ and OXTR group are significant predictors of BDNF methylation. In the G-OXTR type, the high CTQ group showed a greater BDNF methylation level. As for the PTSD group, no interaction or moderation effects were found. LimitationsThe present study did not control the dosage, duration of medications, and different trauma types and the assessment of childhood trauma was based on self-report. ConclusionsThese results suggested that childhood traumatic experience showed a significant impact on BDNF methylation, and OXTR genes have a moderating effect on this epigenetic mechanism in people who have experienced the childhood traumatic episodes.

A Neurobiological Framework for the Therapeutic Potential of Music and Sound Interventions for Post-Traumatic Stress Symptoms in Critical Illness Survivors

Overview: Post traumatic stress disorder (PTSD) has emerged as a severely debilitating psychiatric disorder associated with critical illness. Little progress has been made in the treatment of post-intensive care unit (ICU) PTSD. Aim: To synthesize neurobiological evidence on the pathophysiology of PTSD and the brain areas involved, and to highlight the potential of music to treat post-ICU PTSD. Methods: Critical narrative review to elucidate an evidence-based neurobiological framework to inform the study of music interventions for PTSD post-ICU. Literature searches were performed in PubMed and CINAHL. The Scale for the Assessment of Narrative Review Articles (SANRA) guided reporting. Results: A dysfunctional HPA axis feedback loop, an increased amygdalic response, hippocampal atrophy, and a hypoactive prefrontal cortex contribute to PTSD symptoms. Playing or listening to music can stimulate neurogenesis and neuroplasticity, enhance brain recovery, and normalize stress response. Additionally, evidence supports effectiveness of music to improve coping and emotional regulation, decrease dissociation symptoms, reduce depression and anxiety levels, and overall reduce severity of PTSD symptoms. Conclusions: Despite the lack of music interventions for ICU survivors, music has the potential to help people suffering from PTSD by decreasing amygdala activity, improving hippocampal and prefrontal brain function, and balancing the HPA-axis.

A Narrative Review of the Association between Post-Traumatic Stress Disorder and Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) and post-traumatic stress disorder (PTSD) are often co-morbid with implications for disease severity and treatment outcomes. OSA prevalence is higher in PTSD sufferers than in the general population, with a likely bidirectional effect of the two illnesses. There is substantial evidence to support the role that disturbed sleep may play in the pathophysiology of PTSD. Sleep disturbance associated with OSA may interfere with normal rapid eye movement (REM) functioning and thus worsen nightmares and sleep-related movements. Conversely, hyperarousal and hypervigilance symptoms of PTSD may lower the arousal threshold and thus increase the frequency of sleep fragmentation related to obstructive events. Treating OSA not only improves OSA symptoms, but also nightmares and daytime symptoms of PTSD. Evidence suggests that positive airway pressure (PAP) therapy reduces PTSD symptoms in a dose-dependent fashion, but also presents challenges to tolerance in the PTSD population. Alternative OSA treatments may be better tolerated and effective for improving both OSA and PTSD. Further research avenues will be introduced as we seek a better understanding of this complex relationship.