There is inconsistency in the literature regarding the nature of hypothalamic-pituitary-adrenal (HPA) axis functionality in post-traumatic stress disorder (PTSD).

Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy.Design Systematic review and meta-analyses of relapse prevention trials.Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016).Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse.Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool.Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients' preferences.

Introduction: Exposure to interpersonal violence (IPV) can lead to post-traumatic stress disorder (PTSD) in mothers, and in turn adversely affect the mother-child relationship during early development, as well as the mental health of their children. Our objectives are to assess: (1) the association of maternal IPV-PTSD to child psychopathology, (2) the association of maternal IPV independently of PTSD to child psychopathology, and (3) the relationship between child exposure to violence to the psychopathology of these children. Methods: We used data from the longitudinal Geneva Early Childhood Stress Project. The sample included 64 children [mean age at Phase 1 = 2.4 (1.0-3.7) years] of mothers with or without IPV-PTSD. Data on mothers was collected during Phase 1, using the Clinical Administered PTSD Scale (CAPS), the Brief Physical and Sexual Abuse Questionnaire (BPSAQ) and the Conflict Tactics Scale (CTS2). Modules of a semi-structured diagnostic interview, and the Violence Exposure Scale were used to collect information on child at Phase 2, when children were older [mean age = 7.02 (4.7-10)]. Results: A higher CAPS score in mothers when children were toddler-age was associated with an increased risk of symptoms of attention deficit/hyperactivity disorder (ADHD; β = 0.33, p = 0.014) and PTSD in school-age children. The association between maternal IPV-PTSD and child PTSD (β = 0.48, p < 0.001) symptoms remained significant after adjustment for potential confounders. Among children, exposure to violence was associated with an increased risk of symptoms of generalized anxiety (β = 0.37, p = 0.006), major depressive (β = 0.24, p = 0.039), ADHD (β = 0.27, p = 0.040), PTSD (β = 0.52, p < 0.001), conduct (β = 0.58, p = 0.003) and oppositional defiant (β = 0.34, p = 0.032) disorders. Conclusion: Our longitudinal findings suggest that maternal IPV-PTSD during the period of child development exert an influence on the development of psychopathology in school-aged children. Mothers' IPV was associated with child psychopathology, independently of PTSD. Child lifetime exposure to violence had an additional impact on the development of psychopathology. Careful evaluation of maternal life-events is essential during early childhood to reduce the risk for the development of child psychopathology. Early efforts to curb exposure to violence in children and early intervention are both needed to reduce further risk for intergenerational transmission of trauma, violence, and related psychopathology.

Previous studies on the impact of the COVID-19 pandemic on the mental health of health-care workers have relied on self-reported screening measures to estimate the point prevalence of common mental disorders. Screening measures, which are designed to be sensitive, have low positive predictive value and often overestimate prevalence. We aimed to estimate prevalence of common mental disorders and post-traumatic stress disorder (PTSD) among health-care workers in England using diagnostic interviews.

A number of studies have been done to investigate the role of brain-derived neurotrophic factor (BDNF) in patients with post-traumatic stress disorder (PTSD). In this study we aimed to test the relationship between plasma BDNF levels and PTSD. We solicited 65 subjects having recently experienced road traffic accidents (RTA) conforming to screening criteria. They were given follow-up examinations after one month, three months, and six months. PTSD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R-TR, American Psychiatric Association, 2000) using the Mini International Neuropsychiatric Interview (MINI). All participants were divided into two groups: a group with PTSD and a group without PTSD. There were no significant differences in plasma BDNF levels between the two groups at either the 48h or six-month examination. Within the PTSD group, no significant differences were found in plasma BDNF levels between the two examinations. BDNF levels in those without PTSD showed a higher trend over time after trauma. Higher BDNF levels may be an important protective factor for the prevention of traumatized subjects from developing PTSD.

Previous work has demonstrated the relatively high prevalence of risk factors for cognitive impairment, such as sleep disordered breathing (SDB) and obesity, in Vietnam War era veterans with post-traumatic stress disorder (PTSD). No data are currently available on the longitudinal stability of SDB as a risk factor for cognitive decline in that population, which this study now reports.

The extraordinary situation of the 2019-2022 pandemic caused a dramatic jump in the incidence of post-traumatic stress disorder (PTSD). PTSD is currently regarded not only as a neuropsychiatric disorder, but also as a comorbidity accompanied by cardiovascular diseases, circulatory disorders, liver dysfunction, etc. The relationship between behavioral disorders and the degree of morphofunctional changes in the liver remains obscure. In this study, PTSD was modeled in sexually mature male Wistar rats using predatory stress induced by a prey's fear for a predator. Testing in an elevated plus maze allowed the rat population to be divided into animals with low-anxiety (LAP) and high-anxiety (HAP) phenotypes. It was found that morphofunctional analysis of the liver, in contrast to its biochemical profiling, provides a clearer evidence that predatory stress induces liver dysfunction in rats of both phenotypes. This may indicate a decrease in the range of compensatory adaptive reactions in stressed animals. However, in HAP rats, the level of morphofunctional abnormalities in the mechanisms responsible for carbohydrate-fat, water-electrolyte and protein metabolism in the liver testified the prenosological state of the organ, while further functional loading and resulting tension of the regulatory systems could lead to homeostatic downregulation. Meanwhile, the liver of LAP animals was only characterized by insignificant diffuse changes. Thus, we demonstrate here a link between behavioral changes and the degree of morphofunctional transformation of the liver.

Post-traumatic stress disorder (PTSD) is a chronic syndrome triggered by exposure to trauma and a failure to recover from a normal negative emotional reaction to traumatic stress. The neurobiology of PTSD and the participation of neuropeptides in the neural systems and circuits that control fear and anxiety are not fully understood. The long-term dysregulation of neuropeptide systems contributes to the development of anxiety disorders, including PTSD. The neuropeptide galanin (Gal) and its receptors participate in anxiety-like and depression-related behaviors via the modulation of neuroendocrine and monoaminergic systems. The objective of this research was to investigate how Gal expression changes in the brain of rats 2 weeks after exposure to footshock. Rats exposed to footshocks were subdivided into high responders (HR; immobility>60%) and low responders (LR; immobility<40%) based on immobility elicited by a novel tone one day after exposure. On day 14, rats were anesthetized, and the amygdala, hypothalamus, pituitary and adrenal glands were removed for analysis using real-time polymerase chain reaction (RT-PCR). Gal mRNA levels were increased in the amygdala and hypothalamus of HR compared with the control and LR. In contrast, Gal mRNA levels were decreased in the adrenal and pituitary glands of HR compared with the control and LR. Thus, the differential regulation (dysregulation) of the neuropeptide Gal in these tissues may contribute to anxiety and PTSD development.

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

Early life maltreatment is a risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Post-traumatic stress disorder is a severe and heterogeneous disorder with fluctuating states of emotional over- and undermodulation, including hypervigilance, dissociation, and emotion regulation deficits. The perception and regulation of emotions have been linked to interoception, the cortical representation and sensing of inner bodily processes. Although first therapeutic approaches targeting bodily sensations have been found effective in patients with PTSD, and deficits in interoceptive signal representation have been reported in other trauma-related disorders, such as borderline personality disorder (BPD), the role of interoception remains largely unexplored for PTSD.

Converging evidence indicates that orexins (ORXs), the regulatory neuropeptides, are implicated in anxiety- and depression-related behaviors via the modulation of neuroendocrine, serotonergic, and noradrenergic systems. This study evaluated the role of the orexinergic system in stress-associated physiological responses in a controlled prospective animal model. The pattern and time course of activation of hypothalamic ORX neurons in response to predator-scent stress (PSS) were examined using c-Fos as a marker for neuronal activity. The relationship between the behavioral response pattern 7 days post-exposure and expressions of ORXs was evaluated. We also investigated the effects of intracerebroventricular microinfusion of ORX-A or almorexant (ORX-A/B receptor antagonist) on behavioral responses 7 days following PSS exposure. Hypothalamic levels of ORX-A, neuropeptide Y (NPY), and brain-derived neurotrophic factor (BDNF) were assessed. Compared with rats whose behaviors were extremely disrupted (post-traumatic stress disorder [PTSD]-phenotype), those whose behaviors were minimally selectively disrupted displayed significantly upregulated ORX-A and ORX-B levels in the hypothalamic nuclei. Intracerebroventricular microinfusion of ORX-A before PSS reduced the prevalence of the PTSD phenotype compared with that of artificial cerebrospinal fluid or almorexant, and rats treated with almorexant displayed a higher prevalence of the PTSD phenotype than did untreated rats. Activated ORX neurons led to upregulated expressions of BDNF and NPY, which might provide an additional regulatory mechanism for the modulation of adaptive stress responses. The study indicates that the activated ORX system might promote adaptive responses to PSS probably via stimulation of BDNF and NPY secretion, and early intervention with ORX-A reduces the prevalence of the PTSD phenotype and increases the prevalence of adaptive phenotypes. The findings provide some insights into the mechanisms underlying the involvement of the ORX system in stress-related disorders.

Dysregulation of circulating microRNAs (miRNAs) in body fluids has been reported in psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and post-traumatic stress disorder (PTSD). Recent studies of various diseases showed that extracellular vesicles (EV) in body fluids can provide different spectra of circulating miRNAs and disease-associated signatures from whole fluid or EV-depleted fraction. However, the association of miRNAs in EVs to PTSD has not been studied. In this study, we performed a comprehensive profiling of miRNAs in whole plasma, extracellular vesicles (EV) and EV-depleted plasma (EVD) samples collected from combat veterans with PTSD and matched controls by utilizing a next-generation sequencing (NGS) platform. In total, 520 circulating miRNAs were quantified from 24 male Iraq and Afghanistan combat veterans with (n = 12) and without (n = 12) PTSD. The overall miRNA profiles in whole plasma, EV and EVD fractions were different and miRNAs affected by PTSD were also distinct in each sample type. The concentration changes of miR-203a-3p in EV and miR-339-5p in EVD were confirmed in an independent validation cohort that consisted of 20 veterans (10 with and 10 without PTSD) using qPCR. The target genes of these two miRNAs were involved in signaling pathways and comorbid conditions associated with PTSD (e.g., neurotransmitter systems such as dopaminergic and serotonergic signaling, inflammatory response, and cardiovascular diseases). Our findings suggest that PTSD may have different impacts on miRNAs encapsulated in vesicles and outside of vesicles. Further studies using larger samples are needed to evaluate the utility of these miRNAs as diagnostic biomarkers for PTSD.

The current situation in Afghanistan makes it likely that we are facing a new wave of Afghan refugees, warranting more knowledge about how to deal with mental health problems among them. This study aims to gain more knowledge on Explanatory Models (EM) of depression and post-traumatic stress disorders (PTSD) among Afghan refugees resettled in Norway.

Post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder (SAD) all bear the core symptom of anxiety and are separately classified in the new DSM-5 system. The aim of the present study is to obtain evidence for neuroanatomical difference for these disorders. We applied voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie to compare gray matter volume (GMV) in magnetic resonance images obtained for 30 patients with PTSD, 29 patients with OCD, 20 patients with SAD, and 30 healthy controls. GMV across all four groups differed in left hypothalamus and left inferior parietal lobule and post hoc analyses revealed that this difference is primarily due to reduced GMV in the PTSD group relative to the other groups. Further analysis revealed that the PTSD group also showed reduced GMV in frontal lobe, temporal lobe, and cerebellum compared to the OCD group, and reduced GMV in frontal lobes bilaterally compared to SAD group. A significant negative correlation with anxiety symptoms is observed for GMV in left hypothalamus in three disorder groups. We have thus found evidence for brain structure differences that in future could provide biomarkers to potentially support classification of these disorders using MRI.

Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of psychotherapy for PTSD is unresolved.

Traumatic injury is strongly associated with long-term mental health disorders, but the risk factors for developing these disorders are poorly understood. We report on a multi-institutional collaboration to collect long-term patient-centered outcomes after trauma, including screening for post-traumatic stress disorder. The objective of this study is to determine the prevalence of and risk factors for the development of post-traumatic stress disorder after traumatic injury.

"Soldier's Heart," is an American Civil War term linking post-traumatic stress disorder (PTSD) with increased propensity for cardiovascular disease (CVD). We have hypothesized that there might be a quantifiable genetic basis for this linkage. To test this hypothesis we identified a comprehensive set of candidate risk genes for PTSD, and tested whether any were also independent risk genes for CVD. A functional analysis algorithm was used to identify associated signaling networks. We identified 106 PTSD studies that report one or more polymorphic variants in 87 candidate genes in 83,463 subjects and controls. The top upstream drivers for these PTSD risk genes are predicted to be the glucocorticoid receptor (NR3C1) and Tumor Necrosis Factor alpha (TNFA). We find that 37 of the PTSD candidate risk genes are also candidate independent risk genes for CVD. The association between PTSD and CVD is significant by Fisher's Exact Test (P = 3 × 10-54). We also find 15 PTSD risk genes that are independently associated with Type 2 Diabetes Mellitus (T2DM; also significant by Fisher's Exact Test (P = 1.8 × 10-16). Our findings offer quantitative evidence for a genetic link between post-traumatic stress and cardiovascular disease, Computationally, the common mechanism for this linkage between PTSD and CVD is innate immunity and NFκB-mediated inflammation.

We aimed to investigate depression, anxiety, stress, and PTSD symptoms and their relationship with disease severity in acutely ill hospitalized Coronavirus disease 2019 (COVID-19) patients. A single-center cross-sectional observational survey study screening for psychiatric symptoms using the Depression, Anxiety and Stress Scale-21 Items (DASS-21) and the Impact of Events Scale-Revised (IES-R) questionnaires was performed including a total of 169 acutely ill COVID-19 patients. All patients were adults and of white race and developed respiratory insufficiency during hospitalization. Demographic, clinical and laboratory data were evaluated as predictors of psychiatric symptoms. We hypothesized that higher intensity of COVID-19 symptoms and higher oxygen requirement would be associated with occurrence of depression, anxiety, stress, and PTSD symptoms. Depressive symptoms were absent in 29%, mild in 16%, moderate in 27.8%, severe in 10.7% and extremely severe in 16.6% patients. Anxiety symptoms were absent in 43.8%, mild in 6.5%, moderate in 17.2%, severe in 5.3% and extremely severe in 27.2% patients. Stress symptoms were absent in 78.7%, mild in 4.7%, moderate in 7.1%, severe in 7.7%, and extremely severe in 1.8% patients. A total of 60.9% patients had no PTSD symptoms, 16% had undiagnosed symptoms, and 23.1% met the criteria for a PTSD diagnosis. All psychiatric symptoms were more pronounced in female patients, depression and anxiety symptoms were associated with prior chronic obstructive pulmonary disease. Only depressive symptoms were significantly associated with higher intensity of COVID-19 symptoms and higher oxygen requirement. Acutely ill hospitalized COVID-19 patients presented a high prevalence of emergent psychiatric sequelae, especially in females, and more severe COVID-19 influenced mostly the severity of depressive symptoms.

The development of optimal classification criteria for specific mental disorders which share similar symptoms is an important issue for precise diagnosis. We investigated whether P300 features in both sensor-level and source-level could be effectively used to classify post-traumatic stress disorder (PTSD) and major depressive disorder (MDD).

Pediatric injury is highly prevalent and has significant impact both physically and emotionally. The majority of pediatric injuries are treated in emergency departments (EDs), where treatment of physical injuries is the main focus. In addition to physical trauma, children often experience significant psychological trauma, and the development of acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) is common. The consequences of failing to recognize and treat children with ASD and PTSD are significant and extend into adulthood. Currently, screening guidelines to identify children at risk for developing these stress disorders are not evident in the pediatric emergency setting. The goal of this systematic review is to summarize evidence on the psychometric properties, diagnostic accuracy, and clinical utility of screening tools that identify or predict PTSD secondary to physical injury in children. Specific research objectives are to: (1) identify, describe, and critically evaluate instruments available to screen for PTSD in children; (2) review and synthesize the test-performance characteristics of these tools; and (3) describe the clinical utility of these tools with focus on ED suitability.