Higher risk-less data: A systematic review and meta-analysis on the role of sex and gender in trauma research.

Women and men are at different risk for posttraumatic stress disorder (PTSD). It is unclear, however, how studies on PTSD risk factors integrate this knowledge into their research. Moreover, the temporal development of women's higher PTSD risk is unknown. In this systematic review and meta-analysis, we examine how prospective studies on PTSD development (k = 47) consider sex and gender across four domains (samples, terminology, analyses, and reporting). Further, we differentially analyze sex/gender differences within five time intervals from 1 month to 5 years posttrauma. PTSD prevalence (OR = 1.72 [1.27-2.34]) and severity (g = 0.31 [0.09, 0.53]) were increased for women relative to men at 1 month posttrauma already, that is, at the first timepoint of a possible PTSD diagnosis. PTSD severity was elevated for women compared to men across all time intervals, but evidence for increased PTSD prevalence for women relative to men was less stable with longer follow-ups. Despite women's higher PTSD burdens, they were clearly underrepresented in samples (68.3% male, 31.7% female participants). Only 5.0% of studies explained or described their understanding of sex and gender, and only 2.6% used sex as discovery variable, that is, investigating sex-dependent risk mechanisms. Sex and gender aspects in design, data, and discussion were considered by only one-third of studies each. Trauma research falls short of its potential to adequately consider sex and gender. Sex- and gender-sensitive practices can advance rigor, innovation, and equity in psychopathology research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Higher Depressive Symptoms in Irregular Menstrual Cycles: Converging Evidence from Cross-Sectional and Prospective Assessments.

BACKGROUND: Menstrual cycle regularity is an important marker of reproductive health and associated with physiological and psychological illnesses, as well as experiencing stress. We hypothesized that individuals with irregular menstrual cycles report higher depressive symptom severity, after controlling for stress occurrence. METHODS: The hypothesis was examined through two measurement approaches: a cross-sectional and a prospective, longitudinal study. In the cross-sectional study, participants (n = 394) reported depressive symptoms and their overall menstrual cycle regularity. In the longitudinal study, participants (n = 77) completed questionnaires on depressive symptoms and stress during the mid-follicular and periovulatory phase of one menstrual cycle. Depressive symptoms were compared between participants with regular and irregular cycles through a Welch t test and an ANCOVA. RESULTS: Participants with irregular menstrual cycles reported more depressive symptoms in the cross-sectional analysis. Similarly, in the longitudinal analysis, the group with a current irregular menstrual cycle reported more depressive symptoms after controlling for stress occurrence. When including only complete data sets without multiple imputation (n = 52), the direction of the effects remained but did not reach statistical significance. CONCLUSIONS: The results indicate an association between depressive symptoms and menstrual cycle irregularity. Limitations were that although we investigated the menstrual cycle prospectively, it would have been more precise to include two or more cycles and daily sex hormone measurements. Further limitations were the suboptimal statistical power and the data collection during the COVID pandemic. We give recommendations on how to incorporate the association of depressive symptoms and cycle irregularity in future study designs on women's mental health.

Cortisol response to traumatic stress to predict PTSD symptom development - a systematic review and meta-analysis of experimental studies.

Background: Pre-and post-traumatic hypothalamic-pituitary-adrenal (HPA) axis markers have been studied to predict posttraumatic stress disorder (PTSD) risk, but its acute reactivity cannot be measured in real-life settings. Experimental paradigms can depict the cortisol response to stimuli that simulate traumatic events.Objective: To review experimental studies on the cortisol response to traumatic stimuli and the correlation between cortisol and PTSD symptoms.Method: Experimental, (un-)published studies in German or English from any year were eligible if they confronted non-traumatized humans with traumatic stimuli, assessed cortisol before, during or after stimulus presentation and subsequent PTSD symptoms. The literature was searched via PubMed, PubPsych, PsychINFO, PsycArticle, Web of Science, EMBASE, ProQuest and ClinicalTrials.gov up to 16th February 2021. Risk of bias was assessed with the Cortisol Assessment List. Multilevel-meta-analyses were conducted under the random effects model. The standardized mean change (dSMC) indicated the cortisol response. Coefficient r indicated the correlations between cortisol and PTSD symptoms.Results: 14 studies, investigating 1004 individuals, were included. A cortisol response was successfully induced between 21 and 40 min post-presentation onset (kobservations = 25, dSMC = 0.15 [.03; .26]). Cortisol was not associated with overall or cluster-level PTSD symptoms. On a symptom-level, higher pre-presentation onset cortisol was correlated with lower state tension (k = 8, r = -.18 [-.35; -.01]), higher state happiness (k = 8, r = -.34 [-.59; -.03], variable inverted) and lower state anger (k = 9, r = -.14 [-.26; -.01]). Higher post-presentation onset cortisol was correlated with higher state happiness (k = 16, r = -.20 [-.33; -.06]) and lower state sadness (k = 17, r = -.16 [-.25; -.05]), whereas cortisol response was positively correlated with state anxiety (k = 9, r = .16 [0.04; 0.27]).Conclusions: Experimental paradigms effectively induce a cortisol response. Higher basal cortisol, higher cortisol, as measured after traumatic stimulus presentation, and a lower cortisol response were associated with more adaptive emotional reactions. These markers did not predict longer-term PTSD symptoms.

Experimental trauma paradigms successfully induced a cortisol response.Cortisol was predictive for single state, emotion-related symptoms, but not overall PTSD symptoms.Trauma paradigms shed light into the immediate post-trauma period that is hard to capture in real life, but the gap between experimental and naturalistic settings is difficult to overcome.

Menstrual cycle-related changes in HPA axis reactivity to acute psychosocial and physiological stressors - A systematic review and meta-analysis of longitudinal studies.

Sex disparities are evident in the biological response to acute stressors, with a suggested influence of ovarian hormones on hypothalamic-pituitary-adrenal (HPA) axis functioning. This systematic review and meta-analysis investigates differences in HPA axis reactivity to acute psychosocial or physiological stressors between menstrual cycle phases. A systematic literature search of six databases resulted in 12 longitudinal studies (n = 182) examining HPA axis reactivity in healthy, naturally-cycling, non-breastfeeding participants aged between 18 and 45 years in at least two cycle phases. The quality of cortisol and menstrual cycle assessment was rated and a descriptive synthesis and meta-analysis of HPA axis reactivity between two broader and five more precise cycle phases was conducted. Three studies provided sufficient data for the meta-analysis and showed a significant, small-sized effect, indicating higher cortisol reactivity in the luteal than in the follicular cycle phase. More primary studies with high-quality menstrual cycle and cortisol assessment are needed. The review did not receive funding and was pre-registered (PROSPERO; CRD42020181632).

The effect of an internet-based intervention for depression on cortisol and alpha-amylase.

INTRODUCTION: Psychotherapeutic interventions for major depressive disorder (MDD) have been suggested to be associated with a normalization of biological stress system (i.e., the hypothalamic-pituitary-adrenal axis and the autonomic nervous system) dysregulation. Furthermore, pre-intervention cortisol parameters have been identified as prescriptive biological markers of treatment success. However, evidence of treatment effects on the biological stress systems is still sparse, and results are heterogeneous. The current study examined the effect of an internet-based intervention for MDD on salivary cortisol and alpha-amylase as well as hair cortisol concentrations. Moreover, the prescriptive capacity of pre-intervention cortisol and alpha-amylase concentrations on treatment response was explored. METHODS: Thirty-eight participants suffering from mild to moderate MDD collected saliva and hair samples throughout the intervention. Biological outcome parameters were salivary cortisol and alpha-amylase (awakening response, total diurnal output, diurnal slope) and hair cortisol concentrations. Treatment response was indicated by change in depression severity and perceived chronic stress. RESULTS: Treatment response on depression scores or chronic stress was not associated with changes in any of the cortisol or alpha-amylase parameters. Exploratory analysis indicated that non-responders showed a steeper alpha-amylase slope pre-intervention. DISCUSSION: The results indicate that changes in depressive symptoms did not correspond to changes of the biological stress systems, contradicting the suggested normalization of dysregulated hypothalamic-pituitary-adrenal axis or autonomic nervous system activity through a psychotherapeutic intervention. However, the results point to a potential role of pre-intervention alpha-amylase slope as a prescriptive marker of treatment response for depression.

Biological markers in clinical psychological research - A systematic framework applied to HPA axis regulation in PTSD.

Biological markers, particularly endocrine measurements, are increasingly being integrated into clinical psychological research. We introduce a systematic framework that classifies different functions of such biomarkers. The framework distinguishes between diagnostic biomarkers which add a biological perspective to conventional clinical assessments, prognostic biomarkers that inform about an individual's risk to develop or maintain a mental health disorder, and intervention-related biomarkers. Regarding interventions, including prevention and treatment, it further distinguishes between prescriptive biomarkers which predict an individual's response to an intervention, outcome biomarkers which evaluate intervention-related changes on a biological level and indicators of change mechanisms. We demonstrate how to apply the framework by exemplarily classifying and describing previously published systematic reviews and primary empirical studies on endogenous, peripheral cortisol concentrations as a biomarker for posttraumatic stress disorder (PTSD). The evidence on cortisol's diagnostic and prognostic value is heterogeneous and still sparse regarding parameters based on multiple cortisol measurements, such as the cortisol awakening response. With regard to interventions, most research focused on trauma-focused psychotherapy and cortisol reactivity to trauma reminders. This field of research appears to be growing and very promising due to its potential to optimize PTSD-related interventions. The proposed framework can help in gaining a systematic overview of existing research. It can assist in structuring, comparing, summarizing and evaluating empirical studies, and in identifying research gaps.

The Cortisol Assessment List (CoAL) A tool to systematically document and evaluate cortisol assessment in blood, urine and saliva.

Background: The reliable assessment of cortisol is a necessary requirement to produce replicable research. Several recommendations to increase cortisol assessment reliability exist. However, cortisol assessment methodology is still rather heterogeneous. For this reason, the Cortisol Assessment List (CoAL) was created.The CoAL can be used to guide researchers during the planning phase and document which measures were taken to increase cortisol data reliability in original studies. Moreover, the CoAL can be used to evaluate data quality in meta research. The items representing strategies to obtain reliable cortisol data can be weighted to indicate which are absolutely necessary to consider and which could be applied less restrictively in order to balance data quality and feasibility. In this paper, the construction process of the CoAL is described. Methods: Item synthesis of the CoAL included a literature search to extract empirically based suggestions regarding the reliable assessment of cortisol. Estimates for the item weighting system were obtained by inviting experts in the field to participate in an online survey (n = 25). Inter-rater reliability (IRR) of the CoAL, was determined by letting independent raters use the CoAL to evaluate a set of randomly selected original studies (k = 90). Results: The CoAL was divided into four subscales related to the reporting of sampling procedures, the consideration of state covariates, trait covariates and exclusion criteria. Survey results indicated high agreement among experts for most items (89%) with approximately half of the items in the CoAL being classified as necessary (Cortisol Awakening Response (CAR): 52%; basal cortisol: 52%; reactive cortisol: 44%) in order to obtain reliable cortisol data. Inter-rater agreement was very high (Cohen's Kappa = .98 - 0.99), indicating sufficient psychometric quality of the CoAL. Discussion: The CoAL is the first tool to systematically plan, document and evaluate cortisol assessment. The survey results indicate that the majority of respondents are aware of essential requirements to increase data reliability. However, results were heterogeneous for some items, highlighting the need to start a process of developing a broad scientific consensus regarding reliable cortisol assessment. The implementation of the CoAL could be a first step in this direction. In conclusion, the CoAL reflects empirical evidence and expert knowledge regarding cortisol assessment and can be used as a flexible tool to plan and document empirical studies or evaluate cortisol data quality in meta research.

HPA axis activity across the menstrual cycle - a systematic review and meta-analysis of longitudinal studies.

Differential HPA axis function has been proposed to underlie sex-differences in mental disorders; however, the impact of fluctuating sex hormones across the menstrual cycle on HPA axis activity is still unclear. This meta-analysis investigated basal cortisol concentrations as a marker for HPA axis activity across the menstrual cycle. Through a systematic literature search of five databases, 121 longitudinal studies were included, summarizing data of 2641 healthy, cycling participants between the ages of 18 and 45. The meta-analysis showed higher cortisol concentrations in the follicular vs. luteal phase (dSMC = 0.12, p =.004, [0.04 - 0.20]). Comparisons between more precise cycle phases were mostly insignificant, aside from higher concentrations in the menstrual vs. premenstrual phase (dSMC = 0.17, [0.02 - 0.33], p =.03). In all included studies, nine samples used established cortisol parameters to indicate HPA axis function, specifically diurnal profiles (k = 4) and the cortisol awakening response (CAR) (k = 5). Therefore, the meta-analysis highlights the need for more rigorous investigation of HPA axis activity and menstrual cycle phase.

Trauma-related but not PTSD-related increases in hair cortisol concentrations in military personnel.

Dysregulated hypothalamic-pituitary-adrenal (HPA) axis functioning has been associated with posttraumatic stress disorder (PTSD). The current literature is inconsistent regarding this association, possibly due to confounding influences. Hair cortisol concentrations (HCC) allow for retrospective assessment of cumulative HPA axis secretion over several weeks and are considered a trait-like marker of HPA axis activity. Three groups of active and former German Armed Forces service members, comprising PTSD patients (n = 19), healthy controls with deployment-related trauma exposure (n = 10), and non-deployed healthy controls (n = 10) provided samples for HCC analysis. We observed significantly higher HCC in the PTSD and the deployed compared to the non-deployed group. HCC was neither significantly correlated with perceived chronic stress, nor with PTSD severity within patients. The results suggest a differential impact of trauma exposure on HPA axis activity and highlight the notion of cumulative, retrospective cortisol secretion as a psychobiological indicator of trauma exposure. TRIAL REGISTRATION: Australian Clinical Trials Registry (ACTRN12616000956404).

Sex-differential PTSD symptom trajectories across one year following suspected serious injury.

Background: Recent years have shown an increased application of prospective trajectory-oriented approaches to posttraumatic stress disorder (PTSD). Although women are generally considered at increased PTSD risk, sex and gender differences in PTSD symptom trajectories have not yet been extensively studied. Objective: To perform an in-depth investigation of differences in PTSD symptom trajectories across one-year post-trauma between men and women, by interpreting the general trends of trajectories observed in sex-disaggregated samples, and comparing within-trajectory symptom course and prevalence rates. Method: We included N = 554 participants (62.5% men, 37.5% women) from a multi-centre prospective cohort of emergency department patients with suspected severe injury. PTSD symptom severity was assessed at 1, 3, 6, and 12 months post-trauma, using the Clinician-Administered PTSD Scale for DSM-IV. Latent growth mixture modelling on longitudinal PTSD symptoms was performed within the sex-disaggregated whole samples. Bayesian modelling with informative priors was applied for reliable model estimation, considering the imbalanced prevalence of the expected latent trajectories. Results: In terms of general trends, the same trajectories were observed for men and women, i.e. resilient, recovery, chronic symptoms and delayed onset. Within-trajectory symptom courses were largely comparable, but resilient women had higher symptoms than resilient men. Sex differences in prevalence rates were observed for the recovery (higher in women) and delayed onset (higher in men) trajectories. Model fit for the sex-disaggregated samples was better than for the whole sample, indicating preferred application of sex-disaggregation. Analyses within the whole sample led to biased estimates of overall and sex-specific trajectory prevalence rates. Conclusions: Sex-disaggregated trajectory analyses revealed limited sex differences in PTSD symptom trajectories within one-year post-trauma in terms of general trends, courses and prevalence rates. The observed biased trajectory prevalence rates in the whole sample emphasize the necessity to apply appropriate statistical techniques when conducting sex-sensitive research.

Antecedentes: Los últimos años han demostrado una mayor aplicación de enfoques prospectivos orientados a la trayectoria para el trastorno de estrés postraumático (TEPT). Aunque generalmente se considera que las mujeres tienen un mayor riesgo de TEPT, las diferencias de sexo y género en las trayectorias de los síntomas del TEPT aún no se han estudiado ampliamente.Objetivo: Realizar una investigación en profundidad de las diferencias en las trayectorias de los síntomas del TEPT a lo largo de un año después de un trauma entre hombres y mujeres, interpretando las tendencias generales de las trayectorias observadas en muestras desagregadas por sexo, así como comparar el curso y la evolución de los síntomas dentro de la trayectoria y las tasas de prevalencia.Método: Incluimos N = 554 participantes (62.5% hombres, 37.5% mujeres) de una cohorte prospectiva multicéntrica de pacientes del servicio de urgencias con sospecha de lesión grave. La gravedad de los síntomas del TEPT se evaluó 1, 3, 6 y 12 meses después del trauma, utilizando la Escala de TEPT administrada por un médico para el DSM-IV. Se realizó un modelo de mezcla de crecimiento latente sobre los síntomas longitudinales de TEPT en las muestras desagregadas por sexo y en la muestra completa. Se aplicó un modelo bayesiano con antecedentes informativos para una estimación confiable del modelo, considerando la prevalencia desequilibrada de las trayectorias latentes esperadas.Resultados: En términos de tendencias generales, se observaron las mismas trayectorias para hombres y mujeres, es decir, resiliente, recuperación, síntomas crónicos y aparición tardía. Los cursos de síntomas dentro de la trayectoria fueron en gran medida comparables, pero las mujeres resilientes tenían más síntomas másque los hombres resilientes. Se observaron diferencias por sexo en las tasas de prevalencia para las trayectorias de recuperación (mayor en mujeres) y de inicio tardío (mayor en hombres). El ajuste del modelo para las muestras desagregadas por sexo fue mejor que para la muestra completa, lo que indica la aplicación preferida de la desagregación por sexo. Los análisis de la muestra completa llevaron a estimaciones sesgadas de las tasas de prevalencia de trayectorias generales y específicas por sexo.Conclusiones: Los análisis de trayectoria desagregados por sexo revelaron diferencias limitadas entre los sexos en las trayectorias de los síntomas del TEPT durante el año posterior al trauma en términos de tendencias generales, cursos y tasas de prevalencia. Las tasas de prevalencia de trayectoria sesgada observadas en el conjunto de la muestra enfatizan la necesidad de aplicar técnicas estadísticas apropiadas al realizar investigaciones que tengan en cuenta el sexo.

Attentional bias in German Armed Forces veterans with and without posttraumatic stress symptoms - An eye-tracking investigation and group comparison.

BACKGROUND AND OBJECTIVES: Most eye tracking based paradigms evidence patterns of sustained attention on threat coupled with low evidence for vigilance to or avoidance of threat in posttraumatic stress symptoms (PTSS). Still, eye tracking data on attention bias is particularly limited for military population. This eye tracking study investigated attentional bias in PTSS in a sample of German Armed Forces veterans. METHODS: Veterans with deployment-related PTSS (N = 24), veterans with deployment-related traumatization without PTSS (N = 28), and never-deployed healthy veterans (N = 18) were presented with pairs of combat and neutral pictures, pairs of general threat and neutral pictures, and pairs of emotional and neutral faces. Their eye gazes were tracked during a free viewing task. 3 x 3 x 2 mixed general linear model analyses were conducted. Internal consistency of attention bias indicators was calculated for the entire sample and within groups. RESULTS: Veterans with PTSS dwelled longer on general threat AOIs in contrast to non-exposed controls and shorter on general threat and combat associated neutral AOIs in contrast to both control groups. Veterans with PTSS entered faster to general threat AOIs than non-exposed controls. Veterans with PTSS showed circumscribed higher attention fluctuation in contrast to controls. Internal consistency varied across attention bias indicators. LIMITATIONS: Statistical power was reduced due to recruitment difficulties. CONCLUSIONS: Evidence is provided for the maintenance hypothesis in PTSS. No robust evidence is provided for hypervigilant behavior in PTSS. Findings on attention bias variability remain unclear, calling for more investigations in this field.

Salivary Cortisol and Alpha-Amylase in Posttraumatic Stress Disorder and Their Potential Role in the Evaluation of Cognitive Behavioral Treatment Outcomes.

Alterations in HPA-axis and autonomic nervous system activity have been associated with posttraumatic stress disorder (PTSD) development and maintenance and are potentially associated with trauma-focused cognitive behavioral therapy (TF-CBT) outcomes. We examined the role of salivary cortisol (sCort) and alpha-amylase (sAA) in PTSD and TF-CBT outcomes in German Armed Forces service members (N = 100). Participants categorized as PTSD patients (n = 39), previously deployed healthy controls (n = 33), and nondeployed healthy controls (n = 28) provided diurnal profiles of sCort and sAA; PTSD patients provided samples before, immediately after, and 3 months after an internet-based TF-CBT intervention. No group differences emerged regarding total daily sCort and sAA output or daily slopes, ps = .224-.897, fs = 0.05-0.24. Participants with PTSD demonstrated a significantly attenuated sCort awakening response compared to deployed, p = .021, d = 0.59, but not nondeployed controls, p = .918, d = 0.08. Moreover, a significantly steeper sAA awakening response emerged in PTSD patients, p = .034, d = 0.67, and deployed controls, p = .014, d = 0.80, compared to nondeployed controls. From pretreatment to posttreatment (n = 21) and posttreatment to follow-up (n = 14), stable sCort, ps = .282-.628, fs = 0.34-0.49, and sAA concentrations, ps = .068-.758, fs = 0.24-1.13 paralleled a nonsignificant treatment effect. Both PTSD and trauma exposure were associated with alterations in awakening responses, but further investigation is needed to determine whether the observed correspondence remains when PTSD symptoms significantly decline.

Associations between oxytocin and vasopressin concentrations, traumatic event exposure and posttraumatic stress disorder symptoms: group comparisons, correlations, and courses during an internet-based cognitive-behavioural treatment.

Background: Posttraumatic stress disorder (PTSD) is characterized by impairments in extinction learning and social behaviour, which are targeted by trauma-focused cognitive behavioural treatment (TF-CBT). The biological underpinnings of TF-CBT can be better understood by adding biomarkers to the clinical evaluation of interventions. Due to their involvement in social functioning and fear processing, oxytocin and arginine vasopressin might be informative biomarkers for TF-CBT, but to date, this has never been tested. Objective: To differentiate the impact of traumatic event exposure and PTSD symptoms on blood oxytocin and vasopressin concentrations. Further, to describe courses of PTSD symptoms, oxytocin and vasopressin during an internet-based TF-CBT and explore interactions between these parameters. Method: We compared oxytocin and vasopressin between three groups of active and former male service members of the German Armed Forces (n = 100): PTSD patients (n = 39), deployed healthy controls who experienced a deployment-related traumatic event (n = 33) and non-deployed healthy controls who never experienced a traumatic event (n = 28). PTSD patients underwent a 5-week internet-based TF-CBT. We correlated PTSD symptoms with oxytocin and vasopressin before treatment onset. Further, we analysed courses of PTSD symptoms, oxytocin and vasopressin from pre- to post-treatment and 3 months follow-up, as well as interactions between the three parameters. Results: Oxytocin and vasopressin did not differ between the groups and were unrelated to PTSD symptoms. PTSD symptoms were highly stable over time, whereas the endocrine parameters were not, and they also did not change in mean. Oxytocin and vasopressin were not associated with PTSD symptoms longitudinally. Conclusions: Mainly due to their insufficient intraindividual stability, single measurements of endogenous oxytocin and vasopressin concentrations are not informative biomarkers for TF-CBT. We discuss how the stability of these biomarkers might be increased and how they could be better related to the specific impairments targeted by TF-CBT.

Antecedentes: El trastorno de estrés postraumático (TEPT) se caracteriza por deficiencias en el aprendizaje de extinción y el comportamiento social, que son el objetivo del tratamiento cognitivo conductual centrado en el trauma (TF-CBT). Los fundamentos biológicos de TF-CBT se pueden entender mejor agregando biomarcadores a la evaluación clínica de las intervenciones. Debido a su participación en el funcionamiento social y el procesamiento del miedo, la oxitocina y la arginina vasopresina podrían ser biomarcadores informativos para la TF-CBT, pero hasta la fecha, esto nunca se ha probado.Objetivo: Diferenciar el impacto de la exposición a un evento traumático y los síntomas del TEPT en las concentraciones de oxitocina y vasopresina en la sangre. Además, para describir la evolución de los síntomas del TEPT, la oxitocina y la vasopresina durante una TF-CBT basada en Internet y explorar las interacciones entre estos parámetros.Método: Comparamos la oxitocina y la vasopresina entre tres grupos de militares activos y ex militares de las Fuerzas Armadas Alemanas (n = 100): pacientes con TEPT (n = 39), controles sanos desplegados que experimentaron un evento traumático relacionado con el despliegue (n = 33) y controles sanos no desplegados que nunca experimentaron un evento traumático (n = 28). Los pacientes con TEPT se sometieron a una TF-CBT basada en Internet durante 5 semanas. Correlacionamos los síntomas del TEPT con la oxitocina y la vasopresina antes del inicio del tratamiento. Además, analizamos la evolución de los síntomas del TEPT, la oxitocina y la vasopresina antes y después del tratamiento y el seguimiento de 3 meses, así como las interacciones entre los tres parámetros.Resultados: La oxitocina y la vasopresina no difirieron entre los grupos y no se relacionaron con los síntomas del TEPT. Los síntomas del TEPT fueron muy estables en el tiempo, mientras que los parámetros endocrinos no lo fueron, y tampoco cambiaron en la media. La oxitocina y la vasopresina no se asociaron con los síntomas del TEPT de forma longitudinal.Conclusiones: Principalmente debido a su estabilidad intraindividual insuficiente, las mediciones únicas de las concentraciones de oxitocina y vasopresina endógenas no son biomarcadores informativos para TF-CBT. Discutimos cómo podría aumentarse la estabilidad de estos biomarcadores y cómo podrían relacionarse mejor con las deficiencias específicas a las que se dirige TF-CBT.

Associations Between Difficulties in Emotion Regulation and Post-Traumatic Stress Disorder in Deployed Service Members of the German Armed Forces.

BACKGROUND: Experiencing a traumatic event can lead to post-traumatic stress disorder (PTSD), but not every traumatized person develops PTSD. Several protective and risk factors have been identified in civilians and veterans to explain why some individuals develop PTSD and others do not. However, no research has confirmed the relationship between emotion regulation and PTSD in deployed German Armed Forces service members after a foreign assignment. Previous studies have identified some protective factors, such as social support, social acknowledgment, specific personal values, and posttraumatic growth, as well as risk factors, like moral injury and emotion regulation. Thus, the aim of the present study is to confirm the relationship between emotion regulation and PTSD and to test for factors that are associated with higher severity of PTSD symptoms in such a sample. METHODS: A post-hoc secondary analysis was conducted on data collected in a randomized controlled trial. Participants (N = 72) were male active and former military service members that have returned from deployment and were recruited from the German Armed Forces. These participants were separated into two groups according to PTSD diagnosis based on the results of a structured diagnostic interview. Data from evaluation questionnaires administered upon entry into the study were subjected to a cross-sectional analysis. The measures included the severity of PTSD symptoms, clusters of PTSD symptoms, clinical measures, and several measures assessing PTSD-related constructs. Analyses included the Spearman rank correlation coefficient, X2 tests for nominal data, Mann-Whitney U-tests for non-parametric data, and a mediation analysis. RESULTS: The results of the mediation analysis revealed that difficulties in emotion regulation were significantly associated with the severity of PTSD symptoms, which was mediated by social acknowledgment and experimental avoidance but not by moral injury. The analyses showed that the severity of PTSD symptoms and all clusters of PTSD symptoms were significantly associated with most of the measured constructs in expectable directions. Participants in the PTSD group showed significantly higher mean scores on questionnaires measuring constructs that have been associated with PTSD, like emotion regulation and moral injury. They also showed lower mean scores in questionnaires for social support and social acknowledgment as a victim or survivor than participants in the non-PTSD group. CONCLUSION: The present results show that difficulties in emotion regulation are directly associated with the severity of PTSD symptoms in service members of the German Armed Forces. This association is mediated by social acknowledgment and experimental avoidance, but not by moral injury. Thus, future studies should investigate these potentially crucial factors for better understanding of the development and maintenance of PTSD in service members of the German Armed Forces after deployment to create possible treatment adaptions. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Registry, identifier ACTRN 12616000956404 http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370924.

Early posttraumatic autonomic and endocrine markers to predict posttraumatic stress symptoms after a preventive intervention with oxytocin.

BACKGROUND: Efficient prevention of posttraumatic stress disorder (PTSD) needs to target individuals with an increased risk for adverse outcome after trauma. Prognostic or prescriptive biological markers assessed early posttrauma may inform personalized treatment recommendations. OBJECTIVE: To test prognostic and prescriptive effects of early (posttraumatic) autonomic and endocrine markers on PTSD symptom development. METHOD: Autonomic and endocrine markers were assessed within 12 days posttrauma and before treatment initiation within a randomized placebo-controlled trial investigating repeated oxytocin administration as preventive intervention for PTSD. Linear mixed effects models were used to test the effects of heart rate (variability), resting cortisol, morning cortisol and cortisol awakening response (CAR), cortisol suppression by dexamethasone and resting oxytocin on PTSD symptoms 1.5, 3 and 6 months posttrauma in men (n = 54), women using hormonal contraception (n = 27) and cycling women (n = 19). RESULTS: We found significant prognostic effects of resting oxytocin and cortisol suppression. In women using hormonal contraception, higher oxytocin was associated with higher PTSD symptoms across follow-up. Stronger cortisol suppression by dexamethasone, reflecting increased glucocorticoid receptor feedback sensitivity, was associated with lower PTSD symptoms across follow-up in men, but with higher symptoms at 1.5 months in women using hormonal contraception. These effects were independent of treatment condition. No further significant prognostic or prescriptive effects were detected. CONCLUSION: Our exploratory study indicates that resting oxytocin and glucocorticoid receptor feedback sensitivity early posttrauma are associated with subsequent PTSD symptom severity. Notably, prognostic effects depended on sex and hormonal contraception use, emphasizing the necessity to consider these factors in biomedical PTSD research.

Antecedentes: La prevención eficiente del trastorno de estrés postraumático (TEPT) necesita dirigirse a personas con un mayor riesgo de consecuencias adversas después de un trauma. Los marcadores biológicos pronósticos o preceptivos evaluados tempranamente luego del trauma pueden informar recomendaciones de tratamiento personalizadas.Objetivo: Evaluar los efectos pronósticos y preceptivos de los marcadores tempranos (postraumáticos) autonómicos y endocrinos sobre el desarrollo de síntomas de TEPT.Método: Fueron evaluados marcadores autonómicos y endocrinos dentro de los 12 días postrauma y antes de la iniciación del tratamiento dentro de un estudio aleatorio placebo-control, investigando la administración repetida de oxitocina como intervención preventiva para TEPT. Se utilizaron modelos lineales de efectos mixtos para evaluar los efectos de la frecuencia cardiaca (variabilidad), cortisol en reposo, cortisol matutino y respuesta al despertar de cortisol (CAR por sus siglas en inglés), supresión del cortisol por dexametasona y oxitocina en reposo sobre los síntomas de TEPT a los 1.5, 3 y 6 meses postrauma en hombres (N=54), mujeres que usaban contracepción hormonal (N=27) y mujeres ciclantes (N=19).Resultados: Encontramos efectos pronósticos significativos de la oxitocina en reposo y de la supresión de cortisol. En las mujeres que usaban contracepción hormonal, los niveles de oxitocina más altos se asociaron con más síntomas de TEPT a lo largo del seguimiento. La supresión mayor del cortisol por dexametasona, que refleja una mayor sensibilidad a la retroalimentación del receptor de glucocorticoides, se asoció con menos síntomas de TEPT a lo largo del seguimiento en los hombres, pero con mayores síntomas a los 1.5 meses en las mujeres que usaban contracepción hormonal. Estos efectos fueron independientes de la condición de tratamiento. No se detectaron más efectos pronósticos o preceptivos significativos.Conclusión: Nuestro estudio exploratorio indica que la oxitocina en reposo y la sensibilidad a la retroalimentación del receptor de glucocorticoides tempranamente luego del trauma se asocian con la subsecuente severidad de los síntomas de TEPT. Notablemente, los efectos pronósticos dependen del sexo y del uso de contracepción hormonal, lo que enfatiza la necesidad de considerar estos factores en la investigación biomédica en TEPT.

Evaluation of an internet-based intervention for service members of the German armed forces with deployment-related posttraumatic stress symptoms.

BACKGROUND: The present study was designed to evaluate the efficacy of a therapist-guided internet-based cognitive-behavioral therapy (iCBT) intervention for service members of the German Armed Forces with posttraumatic stress disorder (PTSD). The iCBT was adapted from Interapy, a trauma-focused evidence-based treatment based on prolonged exposure and cognitive restructuring. It lasted for 5 weeks and included 10 writing assignments (twice a week). The program included a reminder function if assignments were overdue, but no multimedia elements. Therapeutic written feedback was provided asynchronously within one working day. METHODS: Male active and former military service members were recruited from the German Armed Forces. Diagnoses were assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Mini-International Neuropsychiatric Interview. Psychopathology was assessed at pre-treatment, post-treatment, and 3-month follow-up. Severity of PTSD was the primary outcome and anxiety was the secondary outcome. Participants were randomly allocated to a treatment group that received iCBT immediately or to a waitlist group that received iCBT after 6 weeks. Due to the overall small sample size (n = 37), the two groups were collapsed for the statistical analyses. Change during the intervention period was investigated using latent-change score models. RESULTS: Improvements in the CAPS-5 were small and not statistically significant. For anxiety, small significant improvements were observed from pre- to follow-up assessment. The dropout rate was 32.3%. CONCLUSIONS: The low treatment utilization and the high dropout rate are in line with previous findings on treatment of service members. The interpretation of the current null results for the efficacy of iCBT is limited due to the small sample size, however for military samples effect estimates were also smaller in other recent studies. Our results demonstrate the need to identify factors influencing treatment engagement and efficacy in veterans. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12616000956404.

Trauma exposure, posttraumatic stress disorder and oxytocin: A meta-analytic investigation of endogenous concentrations and receptor genotype.

Oxytocin's stress-reducing and social functions suggest an involvement in trauma processing and posttraumatic stress disorder (PTSD). We searched PubMed, PubPsych, PsycINFO, PsycARTICLES, Web of Science, ProQuest and ClinicalTrials.gov for studies assessing endogenous oxytocin, oxytocin receptor genotype or methylation in traumatized humans. Eligible studies (k = 66) were systematically described. We meta-analytically compared oxytocin parameters between traumatized and non-traumatized individuals (k = 17) and individuals with and without PTSD (k = 8), and correlated oxytocin with trauma exposure (k = 16) and PTSD symptoms (k = 8). Endogenous oxytocin concentrations did not differ between PTSD patients and healthy individuals. The remaining effects on endogenous oxytocin were heterogeneous. Subgroup analyses identified sampling-related, trauma-related and demographic moderators, resulting in inconsistent or non-significant effects. Methylation data were insufficient for meta-analyses, and meta-analytic genotype results were inconsistent. Unstimulated endogenous oxytocin was not a biomarker for trauma exposure or PTSD. Given the impact of methodology, more basic research on endogenous oxytocin measurements is needed. Future studies might consider the oxytocin stress response and investigate oxytocin longitudinally.

Demographic, sampling- and assay-related confounders of endogenous oxytocin concentrations: A systematic review and meta-analysis.

Studies on endogenous oxytocin concentrations are often criticized for the debatable comparability between specimens and the variation in reported values. We performed meta-regressions on k = 229 studies (n = 12 741 participants), testing whether specimen, extraction, sex, age, time of day, or fasting instructions influenced oxytocin measurements. Predicted oxytocin concentrations differed depending on specimen and extraction: Measurements were extremely high in unextracted blood, compared to extracted blood and other specimens. Measurements were higher in samples with more female participants and higher age. Instructions not to smoke before sampling were correlated with higher oxytocin in unextracted samples. There was no impact of instructions to refrain from eating, drinking, consume caffeine, alcohol or exercising. Oxytocin concentrations increased from morning to afternoon. Our results showed that oxytocin is differentially reflected in blood, saliva, urine and cerebrospinal fluid. Extraction impacts oxytocin measurements, particularly in blood. Considering relevant confounders might increase comparability between studies.

HPA axis regulation in posttraumatic stress disorder: A meta-analysis focusing on potential moderators.

Posttraumatic stress disorder (PTSD) is often associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Previous findings are inconsistent, possibly due to trauma exposure of controls or different hormone measurement methods. We investigated cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) in adults with clinical PTSD under basal or challenged conditions (Prospero registration no. CRD42016041690). A search of PubMed, Scopus, Medline, PsycINFO, Pilots/ProQuest, and Web of Science resulted in 108 included studies (N = 6484). Morning and 24 h cortisol were significantly lower in PTSD than in controls (g = -0.21; 95% CI: -0.42-(-0.01); g = -0.31; CI: -0.60-(-0.03)). Significant cortisol increases occurred after awakening in PTSD (g = 0.40; CI: 0.13-0.67) and in non-exposed controls (g = 0.96; CI: 0.59-1.33). Evening DHEA was significantly higher in PTSD than in non-exposed controls (g = 0.58; CI: 0.17-0.99). All groups showed large cortisol suppression effects after dexamethasone administration. Overall, the potential moderators investigated did not reveal a consistent pattern of HPA alterations.