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1.
Mil Med ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239167

RESUMO

INTRODUCTION: Psychological stress is associated with sedentary behavior, which may impair exercise performance. The aim of our study was to examine the association between psychological stress and physical fitness in military personnel. METHOD: A military cohort of 4080 subjects in Taiwan was used for the analysis. The Brief Symptoms Rating Scale (BSRS-5) includes items of anxiety, depression, hostility, interpersonal sensitivity, and insomnia measured by a five-point Likert-type scale of 0-4. Psychological stress was defined as normal (n = 3657), slight (n = 314), and great (n = 109) by BSRS-5 score ≤5, 6-9, and ≥10, respectively. Aerobic fitness and anaerobic fitness were evaluated by the time of 3000-meter running and the numbers of 2-min sit-ups and 2-min push-ups, respectively. Multiple linear and logistic regression analyses were used to determine the relationship. RESULTS: As compared with normal stress, slight and great stress were positive dose-dependently correlated with 3000-meter running time (ß = 9.09 and 14.44; P = 0.0032 and 0.048, respectively) after adjusting for age, sex, service specialty, body mass index, systolic blood pressure, cigarette smoking, alcohol intake, hemoglobin levels, and exercise frequency. Similarly, those with slight stress were more likely to be the worst 10% performers in the 3000-meter run test relative to the normal individuals (odds ratio and 95% confidence intervals: 1.50, 1.00-2.24). By contrast, there was no relationship of psychological stress with the numbers of 2-min sit-ups and 2-min push-ups. CONCLUSIONS: Our findings suggest that the presence of higher psychological stress on military personnel may reduce their cardiorespiratory fitness but not affect the anaerobic fitness.

2.
Clin Epigenetics ; 12(1): 46, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171335

RESUMO

BACKGROUND: Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD). METHODS: In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72). RESULTS: The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10-6, padj = 0.042). CONCLUSIONS: The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.

3.
Psychother Psychosom ; : 1-13, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32203971

RESUMO

BACKGROUND: Veterans with posttraumatic stress disorder (PTSD) tend to benefit less from evidence-based treatments than other PTSD populations. A novel virtual reality and motion-assisted exposure therapy, called 3MDR, provides treatment in an immersive, personalized and activating context. OBJECTIVE: To study the efficacy of 3MDR for veterans with treatment-resistant PTSD. METHOD: In a randomized controlled trial (n = 43) 3MDR was compared to a non-specific treatment component control group. Primary outcome was clinician-rated PTSD symptoms at baseline, after 3MDR, and at the 12-week and 16-week follow-up (primary end point). Intention-to-treat analyses of covariance and mixed models were applied to study differences between groups at the end point and over the course of intervention, controlling for baseline scores. RESULTS: The decrease in PTSD symptom severity from baseline to end point was significantly greater for 3MDR as compared to the control group, with a large effect size (F[1, 37] = 6.43, p = 0.016, d = 0.83). No significant between-group difference was detected in the course of PTSD symptoms during treatment when including all time points. The dropout rate was low (7%), and 45% of the patients in the 3MDR group improved clinically. The number needed to treat was 2.86. CONCLUSIONS: In this trial, 3MDR significantly decreased PTSD symptoms in veterans with, on average, a history of 4 unsuccessful treatments. The low dropout rate may be indicative of high engagement. However, a lack of significant differences on secondary outcomes limits conclusions that can be drawn on its efficacy and underlines the need for larger phase III trials. These data show emerging evidence for 3MDR and its potential to progress PTSD treatment for veterans (Dutch Trial Register Identifier: NL5126).

4.
J Trauma Stress ; 33(2): 181-189, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32162369

RESUMO

Previous neuroimaging studies on resilience have generally compared resilience and psychopathology after stress exposure, which does not allow for conclusions regarding correlates specific to resilience. The aim of the present study was to investigate resilience-specific correlates in cortical thickness and/or cortical surface area and their correlations with psychometric measurements, using a three-group design that included a non-trauma-exposed control group in order to disentangle effects related to resilience from those related to psychopathology. Structural magnetic resonance imaging scans were acquired from 82 Dutch police officers. Participants were categorized into resilient (n = 31; trauma exposure, no psychopathology), vulnerable (n = 32; trauma exposure, psychopathology), and control groups (n = 19; no trauma exposure, no psychopathology). Specific regions of interest (ROIs) were identified based on previous studies that found the rostral and caudal anterior cingulate cortex (ACC) to be implicated in trauma-related psychopathology. Cortical thickness and surface area of the ROIs-the rostral and caudal ACC-and of the whole brain were examined. No significant differences in cortical thickness or surface area were found between the resilient group and other groups in the ROI and whole-brain analyses. Thus, the results of the present study provide no evidence of an association between resilience to traumatic stress and measures of thickness and surface area in cortical regions of the brain in a sample of Dutch police officers.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32170326

RESUMO

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds, but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, two psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses four types of compounds: 3,4-methylenedioxymethamphetamine (MDMA), ketamine, classical psychedelics (e.g. psilocybin and LSD) and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms, to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research.

6.
Clin Epigenetics ; 12(1): 11, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931860

RESUMO

BACKGROUND: Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-analysis. RESULTS: Stage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 × 10-08) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region. CONCLUSIONS: This study suggests that the development of combat-related PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent findings suggest the involvement of the immune system through the HLA region and HEXDC, and MAD1L1 which was previously associated with PTSD.

8.
Front Genet ; 10: 1042, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824554

RESUMO

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop upon exposure to a traumatic event. While most people are able to recover promptly, others are at increased risk of developing PTSD. However, the exact underlying biological mechanisms of differential susceptibility are unknown. Identifying biomarkers of PTSD could assist in its diagnosis and facilitate treatment planning. Here, we identified serum microRNAs (miRNAs) of subjects that underwent a traumatic event and aimed to assess their potential to serve as diagnostic biomarkers of PTSD. Next-generation sequencing was performed to examine circulating miRNA profiles of 24 members belonging to the Dutch military cohort Prospective Research in Stress-Related Military Operations (PRISMO). Three groups were selected: "susceptible" subjects who developed PTSD after combat exposure, "resilient" subjects without PTSD, and nonexposed control subjects (N = 8 per group). Differential expression analysis revealed 22 differentially expressed miRNAs in PTSD subjects compared to controls and 1 in PTSD subjects compared to resilient individuals (after multiple testing correction and a log2 fold-change cutoff of ≥|1|). Weighted Gene Coexpression Network Analysis (WGCNA) identified a module of coexpressed miRNAs which could distinguish between the three groups. In addition, receiver operating characteristic curve analyses suggest that the miRNAs with the highest module memberships could have a strong diagnostic accuracy as reflected by high areas under the curves. Overall, the results of our pilot study suggest that serum miRNAs could potentially serve as diagnostic biomarkers of PTSD, both individually or grouped within a cluster of coexpressed miRNAs. Larger studies are now needed to validate and build upon these preliminary findings.

9.
Mol Psychiatry ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645664

RESUMO

Epigenetic mechanisms play a role in the detrimental effects of traumatic stress and the development of post-traumatic stress disorder (PTSD). However, it is unknown whether successful treatment of PTSD restores these epigenetic marks. This study investigated longitudinal changes of blood-based genome-wide DNA methylation levels in relation to trauma-focused psychotherapy for PTSD in soldiers that obtained remission (N = 21), non-remitted PTSD patients (N = 23), and trauma-exposed military controls (N = 23). In an independent prospective cohort, we then examined whether these DMRs were also relevant for the development of deployment-related PTSD (N = 85). Successful treatment of PTSD was accompanied by significant changes in DNA methylation at 12 differentially methylated regions (DMRs) in the genes: APOB, MUC4, EDN2, ZFP57, GPX6, CFAP45, AFF3, TP73, UBCLP1, RPL13P, and two intergenic regions (p values < 0.0001 were confirmed using permutation and sensitivity analyses). Of the 12 DMRs related to PTSD symptom reduction, consistent prospective evidence was found for ZFP57 methylation changes related to changing PTSD symptoms (B = -0.84, t = -2.49, p = 0.014). Increasing ZFP57 methylation related to PTSD symptom reduction was present over and above the relation with symptoms, suggesting that psychological treatments exert biological effects independent of symptom reduction. Together, these data provide longitudinal evidence that ZFP57 methylation is involved in both the development and successful treatment of deployment-related PTSD. This study is a first step to disentangle the interaction between psychological and biological systems to identify genomic regions relevant for the etiology and treatment of stress-related disorders such as PTSD.

10.
Eur Neuropsychopharmacol ; 29(12): 1354-1364, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606302

RESUMO

Exposure to traumatic stress increases the odds of developing a broad range of psychiatric conditions. Genetic studies targeting multiple stress-related quantitative phenotypes may shed light on mechanisms underlying vulnerability to psychopathology in the aftermath of stressful events. We applied a multivariate genome-wide association study (GWAS) to a unique military cohort (N = 583) in which we measured biochemical and behavioral phenotypes. The availability of pre- and post-deployment measurements allowed to capture changes in these phenotypes in response to stress. For genome-wide significant loci, we performed functional annotation, phenome-wide analysis and quasi-replication in PTSD case-control GWASs. We discovered one genetic variant reaching genome-wide significant association, surviving permutation and sensitivity analyses (rs10100651, p = 9.9 × 10-9). Functional annotation prioritized the genes INTS8 and TP53INP1. A phenome-wide scan revealed a significant association of these same genes with sleeping problems, hypertension and subjective well-being. Finally, a targeted lookup revealed nominally significant association of rs10100651 in a PTSD case-control GWAS in the UK Biobank (p = 0.02). We provide comprehensive evidence from multiple resources hinting at a role of the highlighted genetic variant in the human stress response, marking the power of multivariate genome-wide analysis of quantitative measures in stress research. Future genetic and functional studies can target this locus to further assess its effects on stress mediation and its possible role in psychopathology or resilience.

11.
Int Rev Psychiatry ; 31(1): 49-59, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31184276

RESUMO

This paper reviews the military context of exposure to combat and deployment in Dutch soldiers. It does so by reviewing war victims and military psychiatry after WWII in the Netherlands, and describes Dutch deployments from the late 1970s to the present. 'Who is the Dutch soldier' is asked to articulate the mental load on the individual soldier before, during, and after deployment. The narrative review of this paper allows one to review how the armed forces personnel is challenged in relation to their specific assignment and in what respect the psychological dimensions are addressed and met in the face of risk and adversity. Finally, some critical considerations for future veterans care programmes are raised.


Assuntos
Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Guerra/psicologia , Adulto , Humanos , Masculino , Países Baixos
13.
J Trauma Dissociation ; 20(5): 564-581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31132959

RESUMO

The inclusion of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reflects the importance of assessing PTSD-DS. We developed the Dissociative Subtype of PTSD Interview (DSP-I). This clinician-administered instrument assesses the presence and severity of PTSD-DS (i.e., symptoms of depersonalization or derealization) and contains a supplementary checklist that enables assessment and differentiation of other trauma-related dissociative symptoms (i.e., blanking out, emotional numbing, alterations in sensory perception, amnesia, and identity confusion). The psychometric properties were tested in 131 treatment-seeking individuals with PTSD and histories of multiple trauma, 17.6 % of whom met criteria for PTSD-DS in accordance with the DSP-I. The checklist was tested in 275 treatment-seeking individuals. Results showed the DSP-I to have high internal consistency, good convergent validity with PTSD-DS items of the CAPS-5, and good divergent validity with scales of somatization, anxiety and depression. The depersonalization and derealization scales were highly associated. Moreover, the DSP-I accounted for an additional variance in PTSD severity scores of 8% over and above the CAPS-5 and number of traumatic experiences. The dissociative experiences of the checklist were more strongly associated with scales of overall distress, somatization, depression, and anxiety than scales of depersonalization and derealization. In conclusion, the DSP-I appears to be a clinically relevant and psychometrically sound instrument that is valuable for use in clinical and research settings.

14.
Animals (Basel) ; 9(5)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100924

RESUMO

The Monash Dog-Owner Relationship Scale (MDORS) is a questionnaire that is used to evaluate the perceived relationship between humans and their dog. This questionnaire was originally only formulated and validated in English, which limits its use among non-English speaking individuals. Although a translation could be made, the translation of questionnaires without additional validation often impairs the reliability of that questionnaire. Therefore, the aim of this study was to validate a translation of the MDORS that is suitable for use among native Dutch speakers. To achieve this, a Dutch translation of the MDORS was made and checked for spelling/grammar mistakes, readability, feasibility, and clarity. A test-retest comparison was subsequently performed on the translation together with a calculation of Cronbach's alpha score and principal component analysis (PCA). Through the PCA, we found that the three-factor model of the original MDORS was also largely present in the Dutch translation. However, deviations were also found, as several questions did not achieve high PCA scores in their original factor. Therefore, we propose that these questions are excluded from the Dutch MDORS.

15.
Mol Psychiatry ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142820

RESUMO

Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30-day-old) stress memory. Here, the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice 1 month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in post mortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.

16.
Mil Med ; 184(11-12): 868-874, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31004149

RESUMO

INTRODUCTION: Soldiers have a higher risk for developing psychiatric disorders that require treatment; often with antidepressants. However, antidepressants as well as the psychiatric disorder, may influence military readiness in several ways. In the general population, early discontinuation of antidepressant treatment is often seen. It is yet unknown whether this occurs to a similar extent in soldiers. The objective of this study was to evaluate discontinuation of antidepressant use by Dutch soldiers in the first 12 months after start and determinants thereof. MATERIALS AND METHODS: Data were obtained from the military pharmacy. All Dutch soldiers who started using an antidepressant between 2000 and 2014 were included. Kaplan-Meier curves were constructed to estimate the discontinuation rate over time and the influence of each determinant on discontinuation rate was estimated using Cox regression. RESULTS: About 25.9% of de 2479 starters had discontinued their antidepressant use after 1 month; after 3 and 6 months this number increased to 52.7% and 70.3%, respectively. Early discontinuation was higher in soldiers who received their first prescription from a neurologist or rehabilitation specialist (HR 1.85, 95% CI 1.55-2.21, HR 2.66 95% CI 1.97-3.58) compared to soldiers with a first prescription from a general practitioner. In addition, early discontinuation was lower in soldiers who were prescribed serotonin reuptake inhibitors and other antidepressants (HR 0.57, 95% CI 0.51-0.60, HR 0.63, 95% CI 0.55-0.73) and in soldiers between 40 and 50 years of age (HR 0.79, 95% CI 0.70-0.89). CONCLUSION: More than half of the soldiers discontinued their prescribed antidepressant within 3 months and after 6 months, only 30% were still on antidepressants.

17.
BMJ Open ; 9(3): e026670, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30842118

RESUMO

PURPOSE: The Prospective Research in Stress-Related Military Operations (PRISMO) study was initiated to gain a better understanding of the long-term impact of military deployment on mental health, and to map the different biological and psychological factors that contribute to the development of stress-related mental health symptoms. PARTICIPANTS: The PRISMO cohort consists of a convenience sample of Dutch military personnel deployed to Afghanistan between 2005 and 2008. Baseline data collection resulted in the recruitment of 1032 military men and women. Combat troops as well as non-combat support troops were recruited to increase the representativeness of the sample to the population as a whole. FINDINGS TO DATE: The prevalence of various mental health symptoms increases after deployment in PRISMO cohort members, but symptom progression over time appears to be specific for various mental health symptoms. For post-traumatic stress disorder, we found a short-term symptom increase within 6 months after deployment (8.2%), and a long-term symptom increase at 5 years after deployment (12.9%). Several biological vulnerability factors associated with the development of stress-related conditions after deployment were identified, including predeployment glucocorticoid receptor sensitivity and predeployment testosterone level. Thus far, 34 publications have resulted from the cohort. FUTURE PLANS: Various analyses are planned that will include the prevalence of mental health symptoms at 10 years postdeployment, as well as trajectory analyses that capture the longitudinal development of symptoms. Furthermore, we will use a machine learning approach to develop predictive and network models for several mental health symptoms, incorporating biological, psychological and social factors.

18.
Eur Neuropsychopharmacol ; 29(3): 405-415, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30773389

RESUMO

Exposure to trauma strongly increases the risk to develop stress-related psychopathology, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). In addition, liability to develop these moderately heritable disorders is partly determined by common genetic variance, which is starting to be uncovered by genome-wide association studies (GWASs). However, it is currently unknown to what extent genetic vulnerability and trauma interact. We investigated whether genetic risk based on summary statistics of large GWASs for PTSD and MDD predisposed individuals to report an increase in MDD and PTSD symptoms in a prospective military cohort (N = 516) at five time points after deployment to Afghanistan: one month, six months and one, two and five years. Linear regression was used to analyze the contribution of polygenic risk scores (PRSs, at multiple p-value thresholds) and their interaction with deployment-related trauma to the development of PTSD- and depression-related symptoms. We found no main effects of PRSs nor evidence for interactions with trauma on the development of PTSD or depressive symptoms at any of the time points in the five years after military deployment. Our results based on a unique long-term follow-up of a deployed military cohort suggest limited validity of current PTSD and MDD polygenic risk scores, albeit in the presence of minimal severe psychopathology in the target cohort. Even though the predictive value of PRSs will likely benefit from larger sample sizes in discovery and target datasets, progress will probably also depend on (endo)phenotype refinement that in turn will reduce etiological heterogeneity.


Assuntos
Transtorno Depressivo/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Campanha Afegã de 2001- , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Modelos Lineares , Masculino , Metanálise como Assunto , Militares/psicologia , Psicopatologia , Adulto Jovem
19.
Eur J Psychotraumatol ; 10(1): 1558705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30693075

RESUMO

Background: Childhood trauma and combat-related trauma are both associated with decreased psychosocial functioning. Coping strategies play an important role in the adjustment to traumatic events. Objective: The present study examined childhood trauma and the mediating role of coping strategies in adult psychological symptoms in a non-clinical military population after deployment to Afghanistan. Additionally, the moderating role of coping strategies in vulnerability to combat events was explored. Method: Participants (N = 932) were drawn from a prospective study assessing psychological complaints (SCL-90), early trauma (ETISR-SF), combat-related events and coping strategies (Brief COPE). Mediation analyses via joint significance testing and moderation analyses were performed. Results: Childhood trauma is related to adult symptoms of general anxiety, depression and problems concerning interpersonal sensitivity through the mediation of self-blame as a coping strategy. Some evidence was found that self-blame moderated vulnerability to combat-related events resulting in psychological complaints, specifically symptoms of anxiety and depression. Conclusions: Military personnel should be made aware of self-criticizing maladaptive belief systems when dealing with aversive events. Negative beliefs about oneself and distorted trauma-related cognitions may have a basis in childhood events. Self-blame cognitions may be a potential mechanism of change in empirically supported trauma interventions such as cognitive processing therapy.

20.
Curr Psychiatry Rep ; 20(12): 118, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30402683

RESUMO

Dissociative experiences have been associated with increased disease severity, chronicity, and, in some cases, reduced treatment response across trauma-related and other psychiatric disorders. A better understanding of the neurobiological mechanisms through which dissociative experiences occur may assist in identifying novel pharmacological and non-pharmacological treatment approaches. Here, we review emerging work on the dissociative subtype of posttraumatic stress disorder (PTSD), and other trauma-related disorders providing evidence for two related overarching neurobiological models of dissociation, the defense cascade model of dissociation and Mobb's threat detection model. In particular, we review neuroimaging studies highlighting alterations in functional connectivity of key brain regions associated with these models, including connectivity between the prefrontal cortex, the amygdala and its complexes, the insula, and the periaqueductal gray. Work implicating the kappa-opioid and endocannabinoid systems in trauma-related dissociative experiences is also reviewed. Finally, we hypothesize mechanisms by which pharmacological modulation of these neurochemical systems may serve as promising transdiagnostic treatment modalities for individuals experiencing clinically significant levels of dissociation. Specifically, whereas kappa-opioid receptor antagonists may serve as a pharmacological vehicle for the selective targeting of dissociative symptoms and associated emotion overmodulation in the dissociative subtype of posttraumatic stress disorder and transdiagnostically, modulation of the endocannabinoid system may reduce symptoms associated with emotional undermodulation of the fight or flight components of the defense cascade model.


Assuntos
Analgésicos Opioides/efeitos adversos , Canabinoides/efeitos adversos , Transtornos Dissociativos/fisiopatologia , Transtornos Dissociativos/psicologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Pesquisa Médica Translacional , Encéfalo/fisiopatologia , Transtornos Dissociativos/induzido quimicamente , Transtornos Dissociativos/terapia , Emoções/efeitos dos fármacos , Humanos , Modelos Neurológicos , Neurobiologia , Transtornos de Estresse Pós-Traumáticos/induzido quimicamente , Transtornos de Estresse Pós-Traumáticos/terapia
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