NTRK2 methylation is related to reduced PTSD risk in two African cohorts of trauma survivors
2020-09-01, Vukojevic, Vanja, Coynel, David, Ghaffari, Navid R., Freytag, Virginie, Elbert, Thomas, Kolassa, Iris-Tatjana, Wilker, Sarah, McGaugh, James L., Papassotiropoulos, Andreas, de Quervain, Dominique J.-F.
Extensive pharmacologic, genetic, and epigenetic research has linked the glucocorticoid receptor (GR) to memory processes, and to risk and symptoms of posttraumatic stress disorder (PTSD). In the present study we investigated the epigenetic pattern of 12 genes involved in the regulation of GR signaling in two African populations of heavily traumatized individuals: Survivors of the rebel war in northern Uganda (n = 463) and survivors of the Rwandan genocide (n = 350). The strongest link between regional methylation and PTSD risk and symptoms was observed for NTRK2, which encodes the transmembrane receptor tropomyosin-related kinase B, binds the brain-derived neurotrophic factor, and has been shown to play an important role in memory formation. NTRK2 methylation was not related to trauma load, suggesting that methylation differences preexisted the trauma. Because NTRK2 methylation differences were predominantly associated with memory-related PTSD symptoms, and because they seem to precede traumatic events, we next investigated the relationship between NTRK2 methylation and memory in a sample of nontraumatized individuals (n = 568). We found that NTRK2 methylation was negatively associated with recognition memory performance. Furthermore, fMRI analyses revealed NTRK2 methylation-dependent differences in brain network activity related to recognition memory. The present study demonstrates that NTRK2 is epigenetically linked to memory functions in nontraumatized subjects and to PTSD risk and symptoms in traumatized populations.
Psychosocial Risk Factors for Child Welfare among Postpartum Mothers with a History of Childhood Maltreatment and Neglect
2016-04-07, Koenig, Alexandra M., Schury, Katharina, Reister, Frank, Köhler-Dauner, Franziska, Schauer, Maggie, Ruf-Leuschner, Martina, Gündel, Harald, Ziegenhain, Ute, Fegert, Jörg, Kolassa, Iris-Tatjana
Background: Childhood maltreatment (CM) can increase the risk of psychosocial risk factors in adulthood (e. g. intimate partner violence, financial problems, substance abuse or medical problems). The transition to parenthood presents those affected by CM with particular challenges, in addition to usual birth-related stressors.
Methods: In this cross-sectional study a total of 240 women were interviewed in the puerperium with respect to CM experiences, using the German version of the Childhood Trauma Questionnaire (CTQ). Current psychosocial risk factors (e. g. financial concerns, maternal mental illness, single parent) were assessed using the Constance Index (KINDEX) for early childhood risk factors. Associations between CM experience and psychosocial risk factors were calculated using simple correlation.
Results: The average age of participants was 33 years. On the CTQ 13.8 % of participants reported emotional abuse, 6.7 % physical abuse and 12.5 % sexual abuse, while 32.1 % reported emotional neglect and 7.5 % physical neglect during childhood. With rising severity of CM, more psychosocial risk factors (KINDEX) were present.
Conclusions: This study shows a clear association between experiences of maltreatment during childhood and the presence of psychosocial stressors among women in the puerperium. Regular screening for a history of CM and parental psychosocial stressors should be conducted early, i.e. during pregnancy, to avoid negative consequences for the child.
Neurobiological Findings in Post-traumatic Stress Disorder
2015, Kolassa, Iris-Tatjana, Illek, Sonja, Wilker, Sarah, Karabatsiakis, Alexander, Elbert, Thomas
Post-traumatic stress disorder (PTSD) symptoms are present across cultures, with the only differences being the indigenous ways in which affected individuals deal with them. Hence, there must be a common underlying basis for these symptoms. The development of an intense memory for the traumatic experiences encountered, and associated neurobiological alterations, may explain the cross-cultural occurrence of similar PTSD symptoms.
This chapter presents selected neurobiological findings in post-traumatic stress disorder (PTSD) in the framework of a neurobiological model of PTSD, the fear network model, which explains the development of strong associative emotional-sensory memories for traumatic events. With repeated exposure to traumatic stressors, this associative network gets strengthened but at the same time detached from the corresponding contextual information. After introducing this theoretical background, we next review current knowledge on genetic risk factors for PTSD development, followed by epigenetic alterations found in trauma survivors with PTSD. This is followed by a section on physiological alterations associated with a diagnosis of PTSD. We elaborate on structural and functional alterations in the brain of trauma survivors with PTSD, which correspond well with the assumptions of the fear network model. Furthermore, we summarize evidence that trauma exposure and subsequent PTSD can have adverse physical health consequences, such as cardiovascular, cerebrovascular, gastrointestinal, musculoskeletal, inflammatory, and autoimmune diseases, and accelerate the aging process, increasing the risk for the earlier onset of age-related diseases. We illustrate on a molecular level which processes increase disease risk in traumatized populations. Finally, we show that at least some PTSD-associated molecular alterations might be reversible through treatment.
Biological memory of childhood maltreatment : current knowledge and recommendations for future research
2012-07, Schury, Katharina, Kolassa, Iris-Tatjana
Child maltreatment (CM) not only has detrimental and lifelong psychological consequences, but also can lead to lasting alterations in core physiological systems—a biologicalmemory ofCM. Furthermore, some of these alterations might even be transmitted to the next generation. This article describes current knowledge about the effects of CM on the stress system (i.e., the hypothalamus–pituitary–adrenal axis), on cellular aging (i.e., telomere length and telomerase activity), and on the immune system. Furthermore, we want to initiate research on the question of transmission of the described physiological alterations subsequent to CM to the next Generation - possibly through epigenetic imprinting. As diverse neurobiological factors and epigenetics are closely linked, these different research fields should join forces to gain a deeper understanding of the biological determinants and sequelae of CM and its transmission.
Alterations of the serum N-glycan profile in female patients with Major Depressive Disorder
2018-02-27, Boeck, Christina, Pfister, Sophia, Bürkle, Alexander, Vanhooren, Valerie, Libert, Claude, Salinas-Manrique, Juan, Dietrich, Detlef E., Kolassa, Iris-Tatjana, Karabatsiakis, Alexander
Glycans are short chains of saccharides linked to glycoproteins that are known to be involved in a wide range of inflammatory processes. As depression has been consistently associated with chronic low-grade inflammation, we asked whether patients with Major Depressive Disorder show alterations in the N-glycosylation pattern of serum proteins that might be linked to associated changes in inflammatory processes.
In a study cohort of 21 female patients with an acute depressive episode and 21 non-depressed female control subjects aged between 50 and 69 years, we analyzed the serum N-glycan profile by DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis (DSA-FACE) and assessed the serum levels of interleukin (IL)− 6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) by chemiluminescence immunoassays and nephelometry.
Compared to controls, MDD patients showed significant differences in the serum levels of several N-glycan structures. Alterations in the serum N-glycan profile were associated with depressive symptom severity and exploratory analyses revealed that they were most pronounced in MDD patients with a history of childhood sexual abuse. Furthermore, MDD patients showed higher levels of IL-6 and a trend for higher CRP levels, which were also associated with similar alterations in the serum N-glycan profile as those characteristic for MDD patients.
The relatively small sample size and the presence of potential confounders (e.g., BMI, smoking, medication).
The results offer the first evidence that specific differences in the N-glycosylation pattern of serum proteins constitute a so far unrecognized level of biological alterations that might be involved in the immune changes associated with MDD.
Metabolite fingerprinting in posttraumatic stress disorder
2016, Koenig, Alexandra Maria, Karabatsiakis, Alexander, Wilker, Sarah, Hamuni, Gilava, Kolassa, Stephan, Renu, Durairaj, Kadereit, Suzanne, Schauer, Maggie, Hennessy, Thomas, Kolassa, Iris-Tatjana
Background: Posttraumatic stress disorder (PTSD) is associated with an increased risk for adverse physical health outcomes. However, the underlying biomolecular processes and associated pathways remain to be further elucidated. The metabolome represents all detectable small bioactive molecules (metabolites) in a given biological sample. Metabolites are the ultimate products of environmentally shaped gene expression and protein activity and are hence closely linked with the individual health status. The untargeted and holistic investigation of the metabolome (termed metabolite fingerprinting) in biological samples might lead to novel insights in PTSD pathophysiology.
Methods: Serum samples from 20 individuals with PTSD and 18 healthy controls were analyzed by liquid chromatography coupled to a Quadrupole/Time-Of-Flight (TOF) mass spectrometer. Groups were matched based on age and ethnicity. Univariate and multivariate approaches, namely Partial Least Square Discriminant Analysis (PLS-DA), were applied for statistical analyses.
Results: The group comparison revealed 13 metabolites, which were significantly altered in PTSD, including four glycerophospholipids and one metabolite involved in endocannabinoid signaling. In the multivariate approach, a metabolite profile of 19 biomolecules predicted PTSD status with an accuracy of 85%.
Conclusions: This study illustrates the potential of metabolite fingerprinting for the identification of novel, trauma and stress-associated pathophysiological underpinning and further provides the possibility to highlight associated biomolecular pathways, such as lipid-derived and endocannabinoid signaling in PTSD.
Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD
2017-03-27, Heck, Angela, Milnik, Annette, Vukojevic, Vanja, Petrovska, Jana, Egli, Tobias, Singer, Jochen, Escobar, Pablo, Kolassa, Iris-Tatjana, Elbert, Thomas, Papassotiropoulos, Andreas
Many mental disorders represent the extremes of the normal distribution of traits, which are related to multiple cognitive and emotional dimensions. By performing whole-exome sequencing of healthy, young subjects with extremely high versus extremely low aversive memory performance, we identified TROVE2 as a gene implicated in emotional memory in health and disease. TROVE2 encodes Ro60, a broadly expressed RNA-binding protein implicated in the regulation of inflammatory gene expression and autoimmunity. A regulatory TROVE2 variant was linked to higher emotional memory capacity and higher emotional memory-related brain activation in healthy subjects. In addition, TROVE2 was associated with traumatic memory and the frequency of post-traumatic stress disorder in genocide survivors.
Stability of auditory event-related potentials in coma research
2015, Schorr, Barbara, Schlee, Winfried, Arndt, Marion, Lulé, Dorothée, Kolassa, Iris-Tatjana, Lopez-Rolon, Alexander, Bender, Andreas
Patients with unresponsive wakefulness syndrome (UWS) or in minimally conscious state (MCS) after brain injury show significant fluctuations in their behavioural abilities over time. As the importance of event-related potentials (ERPs) in the detection of traces of consciousness increases, we investigated the retest reliability of ERPs with repeated tests at four different time points. Twelve healthy controls and 12 inpatients (8 UWS, 4 MCS; 6 traumatic, 6 non-traumatic) were tested twice a day (morning, afternoon) for 2 days with an auditory oddball task. ERPs were recorded with a 256-channel-EEG system, and correlated with behavioural test scores in the Coma Recovery Scale-revised (CRS-R). The number of identifiable P300 responses varied between zero and four in both groups. Reliabilities varied between Krippendorff's α = 0.43 for within-day comparison, and α = 0.25 for between-day comparison in the patient group. Retest reliability was strong for the CRS-R scores for all comparisons (α = 0.83-0.95). The stability of auditory information processing in patients with disorders of consciousness is the basis for other, even more demanding tasks and cognitive potentials. The relatively low ERP-retest reliability suggests that it is necessary to perform repeated tests, especially when probing for consciousness with ERPs. A single negative ERP test result may be mistaken for proof that a UWS patient truly is unresponsive.
The search for peripheral biomarkers for major Depression : Benefiting from successes in the biology of smoking
2014, Philibert, Robert, Gunter, Helen M., Kolassa, Iris-Tatjana
The search for robust, clinically useful markers for major depression (MD) has been relatively unproductive. This is unfortunate because MD is one of the largest socio-economic challenges for much of the world and the development of reliable biomarkers for MD could aid in the prevention or treatment of this common syndrome. In this editorial, we compare the approaches taken in the search for biomarkers for MD to that of the more successful searches for biomarkers for tobacco use, and identify several substantive barriers. We suggest that many of the existing clinical repositories used in these biomarkers searches for MD may be of limited value. We conclude that in the future greater attention should be given to the clinical definitions, characterization of confounding environmental factors and age of subjects included in studies.