Association between Dissociative Symptoms and Morning Cortisol Levels in Patients with Post-traumatic Stress Disorder

Background: Patients with post-traumatic stress disorder (PTSD) showed inconsistencies in their cortisol level, an index of the hypothalamic-pituitary-adrenal (HPA) axis function. This study examined the relationship between dissociation, childhood trauma, and morning cortisol levels in PTSD patients. Methods: This study included 69 patients and 82 healthy controls (HCs). Clinical assessments, including the Childhood Trauma Questionnaire (CTQ) and Peri-traumatic Dissociative Experiences Questionnaire scores (PDEQ), and morning cortisol levels were evaluated. The morning cortisol levels were compared between PTSD with high dissociation (PTSD-HD) and low dissociation (PTSD-LD) groups. The effect of CTQ subtype on morning cortisol levels was analyzed. Outcomes: The PTSD-HD group showed significantly lower cortisol levels than that of the PTSD-LD and HC groups. A significant inverse correlation was found between morning cortisol levels and dissociation. A significant positive correlation was found between dissociation and physical abuse and sexual abuse scores. Morning cortisol levels showed significant positive correlation with emotional abuse, emotional neglect, and physical neglect. There was no moderating or mediating effect of childhood traumatic experience on the relationship between cortisol levels and dissociation. Interpretation: These findings suggest that dissociation is a significant factor related to hypocortisolism in PTSD patients. Additionally, basal morning cortisol levels and dissociation scores were closely associated with the childhood trauma. Funding Statement: This study was supported by a grant from the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2015M3C7A1028252), and a grant from the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (NRF2018R1A2A2A05018505). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: All participants signed an informed consent form approved by the Institutional Review Board before participating (IRB no. 2015-07-025).

INTRODUCTION Evidence shows that posttraumatic stress disorder (PTSD) patients have low basal cortisol levels and glucocorticoid-receptor (GR) supersensitivity following a pharmacological challenge. These findings, however, are controversial, partially due to the presence of confounding factors, such as co-morbidity with major depressive disorder (MDD) and childhood trauma. In the present study, salivary cortisol levels of victims of violence with and without PTSD were assessed following a prednisolone suppression test (PST), controlling for the presence of MDD and sexual abuse during childhood. METHOD The sample was nested in an epidemiological study performed in Sao Paulo City. The subjects with a diagnosis of PTSD (PTSD+) and a matched control group (PTSD-) were submitted to SCID-I; after which Early Trauma Inventory (ETI), Clinician-Administered PTSD Scale (CAPS), Beck Depression (BDI) and Anxiety Inventory (BAI) and the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) were used. Saliva samples were collected before and after 1,5 mg of prednisolone, administered at 10 PM. Discussion These results confirm previous findings that PTSD patients have lower cortisol levels by showing a blunted response to exogenous GC), which is likely due to increased GR responsiveness. Separating the patients with PTSD alone from those with co-morbid MDD showed that hypocortisolism is specific to PTSD, and the presence of MDD counterbalances PTSD-related dysfunction to “normalize” the curve of patients with both diagnoses. The presence of sexual abuse during childhood correlated negatively with lower the salivary cortisol concentrations. Early sexual abuse, but not other types of trauma such as general, physical, and psychological traumas, was correlated with cortisol dysfunction. The presence of sexual abuse during childhood is a potent risk factor for developing an Axis I diagnosis during adulthood [1]. Some authors find a correlation between early abuse and lower cortisol concentrations after a psychosocial stressor test and pharmacological challenge, an effect that is independent of the presence of an Axis I diagnostics [2-3]. The question raised here is whether the presence of severe sexual abuse during childhood and HPA axis response to stress is an endophenotype. Another aspect to consider is whether subjects with a particular type of HPA axis response are at a greater risk for PTSD development after a severe adulthood stressor. PTSD related to increased GR supersensitivity should be investigated further. Research also should address whether the presence of different endophenotypes depends on the timing of the trauma (considering epigenetic phenomenon). Interestingly, we did not find differences between controls and PTSD patients. Despite the fact that 40% of our sample had PTSD+MDD, the presence of PTSD symptoms had a predominant effect on HPA axis by lowering cortisol concentrations, as demonstrated by our comparison of PTSD+ (either with or without MDD) with controls.

Evidence shows that Posttraumatic Stress Disorder (PTSD) patients have low basal cortisol levels and Glucocorticoid-Receptor (GR) super sensitivity following a pharmacological challenge. These findings, however, are controversial, partially due to the presence of confounding factors such as comorbidity with Major Depressive Disorder (MDD) and childhood trauma. In the present study, salivary cortisol levels of victims of violence with and without PTSD were assessed following a Prednisolone Suppression Test (PST), controlling for the presence of MDD and sexual abuse during childhood. The sample was nested in an epidemiological study performed in the city of Sao Paulo. Subjects with a diagnosis of PTSD (PTSD+) and a matched control group (PTSD-) were submitted to the Structured Clinical Interview for DSM-IV, after which the Early Trauma Inventory (ETI), Clinician-Administered PTSD Scale (CAPS), Beck Depression (BDI) and Anxiety Inventory (BAI) and Peri-traumatic Dissociative Experiences Questionnaire (PDEQ) were used. A saliva sample was collected before and after 5 mg of prednisolone was administered at 10 PM. Of the 34 PTSD+ patients, 19 had MDD comorbidity (PTSD+MDD). The cortisol curve of PTSD+MDD patients was similar to that of controls, and both were higher than that of PTSD patients. Cortisol levels after awakening after prednisolone administration were negatively correlated with the CAPS, BAI, and sexual abuse score on the ETI. These findings not only reinforce the idea that PTSD patients have GR super sensitivity, they also reveal that factors such as sexual abuse during childhood and comorbid MDD should be considered when studying HPA-axis reactivity, given their significant impact on the stress response.

Meta-analysis of post-traumatic stress disorder and COVID-19 in patients discharged

BackgroundA dose-dependent effect of Adverse Childhood Experiences (ACE) on the course and severity of psychiatric disorders has been frequently reported. Recent evidence indicates additional impact of type and timing of distinct ACE on symptom severity experienced in adulthood, in support of stress-sensitive periods in (brain) development. The present study seeks to clarify the impact of ACE on symptoms that are often comorbid across various diagnostic groups: symptoms of posttraumatic stress disorder (PTSD), shutdown dissociation and depression. A key aim was to determine and compare the importance of dose-dependent versus type and timing specific prediction of ACE on symptom levels.MethodsExposure to ten types of maltreatment up to age 18 were retrospectively assessed in N = 129 psychiatric inpatients using the Maltreatment and Abuse Chronology of Exposure (MACE). Symptoms of PTSD, shutdown dissociation, and depression were related to type and timing of ACE. The predictive power of peak types and timings was compared to that of global MACE measures of duration, multiplicity and overall severity.ResultsA dose-dependent effect (MACE duration, multiplicity and overall severity) on severity of all symptoms confirmed earlier findings. Conditioned random forest regression verified that PTSD symptoms were best predicted by overall ACE severity, whereas type and timing specific effects showed stronger prediction for symptoms of dissociation and depression. In particular, physical neglect at age 5 and emotional neglect at ages 4–5 were related to increased symptoms of dissociation, whereas the emotional neglect at age 8–9 enhanced symptoms of depression.ConclusionIn support of the sensitive period of exposure model, present results indicate augmented vulnerability by type x timing of ACE, in particular emphasizing pre-school (age 4–5) and pre-adolescent (8–9) periods as sensitive for the impact of physical and emotional neglect. PTSD, the most severe stress-related disorder, varies with the amount of adverse experiences irrespective of age of experience. Considering type and timing of ACE improves understanding of vulnerability, and should inform diagnostics of psychopathology like PTSD, dissociation and depression in adult psychiatric patients.

P-541 - Morning and afternoon levels of serum cortisol in patients with first myocardial infarction and depression

Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse

Aims: Studies in animals and humans suggest that early life stress alters hypothalamus-pituitary-adrenal (HPA) axis activity. The same alterations are related to the symptoms and course of alcohol dependence. This study examined relationships between childhood trauma and HPA axis activity in alcohol-dependent patients controlling for psychopathology and characteristics of dependence. Methods: Thirty-eight consecutive patients (42% female) were examined at admission to detoxification (t1) and 14 days later (t2). Morning plasma levels of cortisol and adrenocorticotropin-releasing hormone (ACTH) were determined. Participants completed the Childhood Trauma Questionnaire (CTQ) and measures of anxiety, depression, and posttraumatic stress disorder. Results: Sexual abuse was related to higher levels of cortisol during acute withdrawal (r = 0.38, p = 0.02). Levels of ACTH were negatively correlated with the CTQ total score (t2: r = –0.42, p < 0.01), emotional abuse (t2: r = –0.33, p = 0.04), emotional neglect (t2: r = –0.33, p = 0.04), and physical neglect (t2: r = –0.33, p = 0.05) controlling for psychopathology and characteristics of dependence. Conclusions: Our findings suggest, that childhood trauma is related to blunted ACTH and increased cortisol during withdrawal in alcohol-dependent patients. Early life stress might be a confounding variable in studies of HPA function in alcohol dependence and future studies should examine potential clinical consequences of these relationships.

Sex differences in the effect of childhood trauma on the clinical expression of early psychosis

This study aimed to determine whether dissociative symptoms and childhood trauma (CT) may help identify a specific subgroup of patients among those hospitalized for alcohol use disorder (AUD). We assessed 587 patients hospitalized for an AUD in a French addiction rehabilitation center (cross-sectional study) regarding dissociative symptoms (DES-taxon), childhood trauma (CTQ), depression (BDI), anxiety (STAI-state and STAI-trait), posttraumatic stress disorder (PTSD; PCL-5), and AUD symptoms (AUDIT). We ran a hierarchical cluster analysis and compared the clusters in terms of dissociation and CT, as well as AUD, depressive, anxiety, and PTSD symptoms. We identified three clusters of patients: (1) patients with low AUD severity and low dissociation (LALD); (2) patients with high AUD severity and low dissociation (HALD); (3) patients with high AUD severity and high dissociation (HAHD). Patients from the HAHD group had significantly higher dissociation and more severe depression, anxiety, and PTSD symptoms than those with LALD and HALD. They also reported more emotional and sexual abuse than those with LALD. Among patients with an AUD, those with high dissociation may constitute an independent subgroup that exhibits a higher prevalence for CT and higher AUD severity, as well as higher depression, anxiety, and PTSD symptoms. Patients with more severe AUD and associated psychiatric symptoms should be systematically screened for dissociation and provided with tailor-based treatments.

PTSD and Combat-Related Injuries: Functional Neuroanatomy

Intimate partner violence (IPV) is often a chronic form of trauma with deleterious mental health problems. Furthermore, IPV survivors have also often experienced trauma in childhood. Consequently, by examining a sample of IPV survivors, this study sought to assess typical trauma sequelae--Posttraumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), or dissociative symptoms-and trauma-related characteristics consistent with Herman's Trauma theory (1992; i.e., chronicity of trauma, age of first trauma exposure, and social support), in relation to hypothalamic-pituitary-adrenal axis function. The study compared basal and diurnal cortisol in women (n = 88) based on diagnostic status and symptom severity (PTSD [n = 14], PTSD and comorbid MDD [n = 43], subthreshold symptoms of PTSD and MDD [n = 19]), dissociative symptoms, and the aforementioned trauma-related characteristics to a matched control group (n = 12) without any lifetime history of mental health diagnoses or exposure to interpersonal trauma. Regardless of their diagnostic status and trauma-related characteristics, trauma-exposed women had higher levels of dissociative symptoms relative to women in the control group, and these dissociative symptoms were inversely related to awakening cortisol levels. Findings suggest that low cortisol levels may not be a diagnostic marker, but instead may be associated with a dissociative coping style developed in the context of trauma exposure, consistent with mechanisms posited by Trauma theory.

In view of evidence of in utero glucocorticoid programming, and our prior observation of lower cortisol levels in 9-month-old infants of mothers with posttraumatic stress disorder (PTSD) compared to mothers without PTSD, we undertook an examination of the effect of in utero maternal stress, as determined by PTSD symptom severity, and maternal cortisol levels on behavioral outcomes in the infant. Ninety-eight pregnant women directly exposed to the World Trade Center (WTC) collapse on 9/11 provided salivary cortisol samples and completed a PTSD symptom questionnaire and a behavior rating scale to measure infant temperament, including distress to limitations, and response to novelty. Mothers who developed PTSD in response to 9/11 had lower morning and evening salivary cortisol levels, compared to mothers who did not develop PTSD. Maternal morning cortisol levels were inversely related to their rating of infant distress and response to novelty (i.e., loud noises, new foods, unfamiliar people). Also, mothers who had PTSD rated their infants as having greater distress to novelty than did mothers without PTSD (t = 2.77, df = 61, P = 0.007). Longitudinal studies are needed to determine how the association between maternal PTSD symptoms and cortisol levels and infant temperament reflect genetic and/or epigenetic mechanisms of intergenerational transmission.

Suicidality, posttraumatic stress, and depressive reactions after earthquake and maltreatment: A cross-sectional survey of a random sample of 6132 chinese children and adolescents

ObjectiveThis study investigated Theory of Mind (ToM) abilities as measured by a hinting task and the Reading the Mind in the Eyes Test (RMET) in individuals diagnosed with post-traumatic strees disorder (PTSD) in relation to different types of childhood trauma and compared to a healthy control group.MethodRMET, a Clinician Administered PTSD Scale (CAPS), a Beck Depression Inventory (BDI), a Childhood Trauma Questionnaire (CTQ), a hinting task, and a socio-demographic questionnaire were administered to PTSD (n=30) patients and healthy controls (n=30).ResultsThere was a significant difference in ToM performance between healthy participants and the PTSD group (p<0.001). A significant correlation was found between trauma types and ToM performance (p<0.01). The diagnosis of PTSD and the severity of PTSD symptoms showed significant correlations with ToM performance (p<0.01). In comparison with the healthy control group, the PTSD group demonstrated lower performance on both ToM tasks. Regardless of the PTSD diagnosis, those people who had a history of childhood trauma had slowed reaction times in response to photographs representing emotionally salient mental states and demonstrated difficulties in the identification of irony/hints in the context of the administered assessment task.ConclusionThe findings of the present study suggest that a diagnosis of PTSD and a history of different types of trauma have an effect on ToM performance. PTSD seems to lead to deterioration in ToM capacities. This may mean that the experience of childhood adversity may lead to long-lasting damage to social cognition. The current study is helpful in that it contributes to a better understanding of the pathogenesis of PTSD; moreover, it will be beneficial in the development of new treatment options. Our research findings suggest that we must concentrate not only on traumatic events during the treatment process of PTSD follow-up and treatment; we must also target deficiencies in cognitive and emotional capabilities.