Prenatal exposure to maternal stress can have lifelong implications for psychological function, such as behavioral problems and even the development of mental illness. Previous research suggests that ...this is due to transgenerational epigenetic programming of genes operating in the hypothalamic-pituitary-adrenal axis, such as the glucocorticoid receptor (GR). However, it is not known whether intrauterine exposure to maternal stress affects the epigenetic state of these genes beyond infancy. Here, we analyze the methylation status of the GR gene in mothers and their children, at 10-19 years after birth. We combine these data with a retrospective evaluation of maternal exposure to intimate partner violence (IPV). Methylation of the mother's GR gene was not affected by IPV. For the first time, we show that methylation status of the GR gene of adolescent children is influenced by their mother's experience of IPV during pregnancy. As these sustained epigenetic modifications are established in utero, we consider this to be a plausible mechanism by which prenatal stress may program adult psychosocial function.
Stress during pregnancy may impact subsequent generations, which is demonstrated by an increased susceptibility to childhood and adulthood health problems in the children and grandchildren. Although ...the importance of the prenatal environment is well reported with regards to future physical and emotional outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Recent studies have identified DNA methylation as a possible mediator of the impact of prenatal stress in the offspring. Whether psychosocial stress during pregnancy also affects DNA methylation of the grandchildren is still not known. In the present study we examined the multigenerational hypothesis, that is, grandmaternal exposure to psychosocial stress during pregnancy affecting DNA methylation of the grandchildren. We determined the genome-wide DNA methylation profile in 121 children (65 females and 56 males) and tested for associations with exposure to grandmaternal interpersonal violence during pregnancy. We observed methylation variations of five CpG sites significantly (FDR<0.05) associated with the grandmother's report of exposure to violence while pregnant with the mothers of the children. The results revealed differential methylation of genes previously shown to be involved in circulatory system processes (FDR<0.05). This study provides support for DNA methylation as a biological mechanism involved in the transmission of stress across generations and motivates further investigations to examine prenatal-dependent DNA methylation as a potential biomarker for health problems.
Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental ...impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic-pituitary-adrenal axis--in particular, the glucocorticoid receptor (hGR) gene--stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.
Posttraumatic stress disorder (PTSD) arises as a long‐term result of exposure to trauma and brings with it an altered autonomic response to potentially threatening stimuli. The present study ...investigates the dynamic sequence of cardiac defense in women with and without PTSD. An acoustic noise of 0.5‐s duration and 105 dB was used to elicit the cardiac defense reaction. The stimulus was repeated three times. Within the PTSD sample, respondents who suffered from more severe PTSD showed a higher heart rate at rest, a higher baseline, and a greater response. Compared to the healthy subjects, the PTSD group showed an elevated heart rate from 6 s to 25 s following the presentation of the first stimulus. There was evidence of habituation in the PTSD group and hints of differential effects on the cardiac defense of traumatic experiences with a high proximity of danger.
With each additional accumulative exposure to severe and traumatic stressors, the likelihood of developing mental health problems and physical diseases increases. Displaced individuals have usually ...experienced a number of serious threats to health due to organized violence in their home country or attacks during the flight. Frequently, domestic violence adds additional strain to the stressors experienced. The resulting impairments in psychosocial functioning reduce the resources needed for social adjustment and integration. Social exclusion then in turn often further aggravates the existing mental health complications. For the treatment of trauma spectrum disorders, different evidence-based psychotherapies are available. In high-income countries, trained and licensed psychotherapists are typically in positions to apply such interventions; however, even an advanced system with a high capacity, such as the psychotherapeutic care offered in Germany, severely struggles to manage the demands associated with the rapid addition of hundreds of thousands of displaced people. Germany's mental healthcare system at present lacks the resources, both human and technological, to effectively manage the present demands. Systematic scientific studies in resource-poor regions of war and conflict have demonstrated that the dissemination of effective treatment to local personnel, even with limited training, results in substantial improvements in the mental health challenges within the community: Organized as a cascade model, members of the refugee community learn to identify weakened fellow citizens requiring in-depth diagnostic interviews. Educated, bilingual individuals acquainted with their country's healthcare system (e. g. nurses, teachers and social workers) receive training to conduct structured interviews and evidence-based interventions under the supervision of centrally organized licensed psychotherapists. More complex cases are referred to local psychotherapists, psychiatrists or specialized treatment centers. These humanitarian efforts are based on the convention for the protection of human rights and secure the safety, freedom and dignity of these persons.
Abstract Background Individuals with trauma-related disorders are complex and heterogeneous; part of this complexity derives from additional psychopathology like dissociation as well as environmental ...adversities such as traumatic stress, experienced throughout the lifespan. Understanding the neurophysiological abnormalities in Post-traumatic stress disorder (PTSD) requires a simultaneous consideration of these factors. Methods Resting state magnetoencephalography (MEG) recordings were obtained from 41 women with PTSD and comorbid depressive symptoms, and 16 healthy women. Oscillatory brain activity was extracted for five frequency bands and 11 source locations, and analyzed in relation to shutdown dissociation and adversity-related measures. Results Dissociative symptoms were related to increased delta and lowered beta power. Adversity-related measures modulated theta and alpha oscillatory power (in particular childhood sexual abuse) and differed between patients and controls. Limitations Findings are based on women with comorbid depressive symptoms and therefore may not be applicable for men or groups with other clinical profiles. In respect to childhood adversities, we had no reliable source for the early infancy. Conclusion Trauma-related abnormalities in neural organization vary with both exposure to adversities as well as their potential to evoke ongoing shutdown responses.
Background: The aim of the present randomized controlled trial was to compare the outcome of 2 active treatments for posttraumatic stress disorder (PTSD) as a consequence of war and torture: ...narrative exposure therapy (NET) and stress inoculation training (SIT). Methods: Twenty-eight PTSD patients who had experienced war and torture, most of them asylum seekers, received 10 treatment sessions of either NET or SIT at the Outpatient Clinic for Refugees, University of Konstanz, Germany. Posttests were carried out 4 weeks after treatment, and follow-up tests were performed 6 months and 1 year after treatment. The main outcome measure was the PTSD severity score according to the Clinician-Administered PTSD Scale (CAPS) at each time point. Results: A significant reduction in PTSD severity was found for NET, but not for SIT. A symptom reduction in the NET group occurred between pretest and the 6-month follow-up examination, the effect size being d = 1.42 (for SIT: d = 0.12), and between pretest and the 1-year follow-up, the effect size being d = 1.59 (for SIT: d = 0.19). The rates and scores of major depression and other comorbid disorders did not decrease significantly over time in either of the 2 treatment groups. Conclusions: The results indicate that exposure treatments like NET lead to a significant PTSD symptom reduction even in severely traumatized refugees and asylum seekers.
Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the ...somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.
Exposure-based therapies are considered the state-of-the-art treatment for Posttraumatic Stress Disorder (PTSD). Yet, a substantial number of PTSD patients do not recover after therapy. In the light ...of the well-known gene × environment interactions on the risk for PTSD, research on individual genetic factors that influence treatment success is warranted. The gene encoding FK506-binding protein 51 (FKBP5), a co-chaperone of the glucocorticoid receptor (GR), has been associated with stress reactivity and PTSD risk. As FKBP5 single-nucleotide polymorphism rs1360780 has a putative functional role in the regulation of FKBP5 expression and GR sensitivity, we hypothesized that this polymorphism influences PTSD treatment success. We investigated the effects of FKBP5 rs1360780 genotype on Narrative Exposure Therapy (NET) outcome, an exposure-based short-term therapy, in a sample of 43 survivors of the rebel war in Northern Uganda. PTSD symptom severity was assessed before and 4 and 10 months after treatment completion. At the 4-month follow-up, there were no genotype-dependent differences in therapy outcome. However, the FKBP5 genotype significantly moderated the long-term effectiveness of exposure-based psychotherapy. At the 10-month follow-up, carriers of the rs1360780 risk (T) allele were at increased risk of symptom relapse, whereas non-carriers showed continuous symptom reduction. This effect was reflected in a weaker treatment effect size (Cohen's D=1.23) in risk allele carriers compared with non-carriers (Cohen's D=3.72). Genetic factors involved in stress response regulation seem to not only influence PTSD risk but also responsiveness to psychotherapy and could hence represent valuable targets for accompanying medication.
The Changing Paradigm of Data-Intensive Computing Kouzes, R.T.; Anderson, G.A.; Elbert, S.T. ...
Computer (Long Beach, Calif.),
2009-Jan., 2009, 2009-01-00, 20090101, Letnik:
42, Številka:
1
Journal Article
Recenzirano
Through the development of new classes of software, algorithms, and hardware, data-intensive applications provide timely and meaningful analytical results in response to exponentially growing data ...complexity and associated analysis requirements.
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