Publications by authors named "Alexander Karabatsiakis"

28 Publications

  • Page 1 of 1

Characterization of the effects of age and childhood maltreatment on DNA methylation.

Dev Psychopathol 2021 Jan 19:1-11. Epub 2021 Jan 19.

Department of Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

DNA methylation of the elongation of very long chain fatty acids protein 2 (ELOVL2) was suggested as a biomarker of biological aging, while childhood maltreatment (CM) has been associated with accelerated biological aging. We investigated the association of age and CM experiences with ELOVL2 methylation in peripheral blood mononuclear cells (PBMC). Furthermore, we investigated ELOVL2 methylation in the umbilical cord blood mononuclear cells (UBMC) of newborns of mothers with and without CM. PBMC and UBMC were isolated from 113 mother-newborn dyads and genomic DNA was extracted. Mothers with and without CM experiences were recruited directly postpartum. Mass array spectrometry and pyrosequencing were used for methylation analyses of ELOVL2 intron 1, and exon 1 and 5' end, respectively. ELOVL2 5' end and intron 1 methylation increased with higher age but were not associated with CM experiences. On the contrary, overall ELOVL2 exon 1 methylation increased with higher CM, but these changes were minimal and did not increase with age. Maternal CM experiences and neonatal methylation of ELOVL2 intron 1 or exon 1 were not significantly correlated. Our study suggests region-specific effects of chronological age and experienced CM on ELOVL2 methylation and shows that the epigenetic biomarker for age within the ELOVL2 gene does not show accelerated biological aging years after CM exposure.
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http://dx.doi.org/10.1017/S0954579420001972DOI Listing
January 2021

Characterization of the effects of age and childhood maltreatment on DNA methylation.

Dev Psychopathol 2021 Jan 19:1-11. Epub 2021 Jan 19.

Department of Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

DNA methylation of the elongation of very long chain fatty acids protein 2 (ELOVL2) was suggested as a biomarker of biological aging, while childhood maltreatment (CM) has been associated with accelerated biological aging. We investigated the association of age and CM experiences with ELOVL2 methylation in peripheral blood mononuclear cells (PBMC). Furthermore, we investigated ELOVL2 methylation in the umbilical cord blood mononuclear cells (UBMC) of newborns of mothers with and without CM. PBMC and UBMC were isolated from 113 mother-newborn dyads and genomic DNA was extracted. Mothers with and without CM experiences were recruited directly postpartum. Mass array spectrometry and pyrosequencing were used for methylation analyses of ELOVL2 intron 1, and exon 1 and 5' end, respectively. ELOVL2 5' end and intron 1 methylation increased with higher age but were not associated with CM experiences. On the contrary, overall ELOVL2 exon 1 methylation increased with higher CM, but these changes were minimal and did not increase with age. Maternal CM experiences and neonatal methylation of ELOVL2 intron 1 or exon 1 were not significantly correlated. Our study suggests region-specific effects of chronological age and experienced CM on ELOVL2 methylation and shows that the epigenetic biomarker for age within the ELOVL2 gene does not show accelerated biological aging years after CM exposure.
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http://dx.doi.org/10.1017/S0954579420001972DOI Listing
January 2021

Associating Emergency Medical Services personnel's workload, trauma exposure, and health with the cortisol, endocannabinoid, and N-acylethanolamine concentrations in their hair.

Sci Rep 2020 12 29;10(1):22403. Epub 2020 Dec 29.

University Psychotherapeutic Outpatient Clinic, Institute of Psychology and Education, Ulm University, 89073, Ulm, Germany.

In their line of duty, Emergency Medical Services (EMS) personnel are exposed to chronically stressful working conditions and recurrent traumatic events, which increase their risk for detrimental health outcomes. Here, we investigated whether this risk is due to altered regulation of the hypothalamus-pituitary-adrenal (HPA) axis and the endocannabinoid system. Therefore, 1 cm hair strands were collected from a cohort of 72 German EMS personnel in order to measure concentrations of cortisol, endocannabinoids [i.e., anandamide (AEA), 2-arachidonoylglycerol (2-AG)], and N-acylethanolamines [i.e., stearoylethanolamide (SEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA)]. Rank correlation analyses were conducted to test associations of cortisol, endocannabinoid, and N-acylethanolamine concentrations with the EMS personnel's workload, lifetime trauma exposure, and mental and physical health problems. We found a negative correlation between cortisol and 2-AG concentrations in hair. Higher hair cortisol was associated with higher workload. Reported traumatic stress during childhood and later in life as well as more severe depressive and physical stress symptoms were associated with elevated 2-AG, SEA, OEA, and PEA concentrations. Future longitudinal research needs to address the prospect of tracing biomolecular markers of glucocorticoid, endocannabinoid, and N-acylethanolamine activity as a predicting value of the long-term course of mental and physical well-being.
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http://dx.doi.org/10.1038/s41598-020-79859-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772331PMC
December 2020

Trauma-focused psychodynamic therapy and STAIR Narrative Therapy of post-traumatic stress disorder related to childhood maltreatment: trial protocol of a multicentre randomised controlled trial assessing psychological, neurobiological and health economic outcomes (ENHANCE).

BMJ Open 2020 12 17;10(12):e040123. Epub 2020 Dec 17.

Institute of Clincal Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.

Introduction: Success rates of psychotherapy in post-traumatic stress disorder related to childhood maltreatment (PTSD-CM) are limited.

Methods And Analysis: Observer-blind multicentre randomised clinical trial (A-1) of 4-year duration comparing enhanced methods of STAIR Narrative Therapy (SNT) and of trauma-focused psychodynamic therapy (TF-PDT) each of up to 24 sessions with each other and a minimal attention waiting list in PTSD-CM. Primary outcome is severity of PTSD (Clinician-Administered PTSD Scale for DSM-5 total) assessed by masked raters. For SNT and TF-PDT, both superiority and non-inferiority will be tested. Intention-to-treat analysis (primary) and per-protocol analysis (secondary). Assessments at baseline, after 10 sessions, post-therapy/waiting period and at 6 and 12 months of follow-up. Adult patients of all sexes between 18 and 65 years with PTSD-CM will be included. Continuing stable medication is permitted. To be excluded: psychotic disorders, risk of suicide, ongoing abuse, acute substance related disorder, borderline personality disorder, dissociative identity disorder, organic mental disorder, severe medical conditions and concurrent psychotherapy. To be assessed for eligibility: n=600 patients, to be e randomly allocated to the study conditions: n=328. Data management, randomisation and monitoring will be performed by an independent European Clinical Research Infrastructure Network (ECRIN)-certified data coordinating centre for clinical trials (KKS Marburg). Report of AEs to a data monitoring and safety board. Complementing study A-1, four inter-related add-on projects, including subsamples of the treatment study A-1, will examine (1) treatment integrity (adherence and competence) and moderators and mediators of outcome (B-1); (2) biological parameters (B-2, eg, DNA damage, reactive oxygen species and telomere shortening); (3) structural and functional neural changes by neuroimaging (B-3) and (4) cost-effectiveness of the treatments (B-4, costs and utilities).

Ethics And Dissemination: Approval by the institutional review board of the University of Giessen (AZ 168/19). Following the Consolidated Standards of Reporting Trials statement for non-pharmacological trials, results will be reported in peer-reviewed scientific journals and disseminated to patient organisations and media.

Trial Registration Number: DRKS 00021142.
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http://dx.doi.org/10.1136/bmjopen-2020-040123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747578PMC
December 2020

Childhood maltreatment is associated with changes in mitochondrial bioenergetics in maternal, but not in neonatal immune cells.

Proc Natl Acad Sci U S A 2020 10 1;117(40):24778-24784. Epub 2020 Oct 1.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, 89081 Ulm, Germany.

Childhood maltreatment (CM) comprises experiences of abuse and neglect during childhood. CM causes psychological as well as biological alterations in affected individuals. In humans, it is hardly explored whether these CM consequences can be transmitted directly on a biological level to the next generation. Here, we investigated the associations between maternal CM and mitochondrial bioenergetics (mitochondrial respiration and intracellular mitochondrial density) in immune cells of mothers and compared them with those of their newborns. In = 102 healthy mother-newborn dyads, maternal peripheral blood mononuclear cells and neonatal umbilical cord blood mononuclear cells were collected and cryopreserved shortly after parturition to measure mitochondrial respiration and intracellular mitochondrial density with high-resolution respirometry and spectrophotometric analyses, respectively. Maternal CM was assessed with the Maternal and neonatal mitochondrial bioenergetics were quantitatively comparable and positively correlated. Female newborns showed higher mitochondrial respiration compared to male newborns. Maternal CM load was significantly and positively associated with mitochondrial respiration and density in mothers, but not with mitochondrial respiration in newborns. Although maternal and neonatal mitochondrial bioenergetics were positively correlated, maternal CM only had a small effect on mitochondrial density in newborns, which was not significant in this study after adjustment for multiple comparisons. The biological relevance of our finding and its consequences for child development need further investigation in future larger studies. This study reports data on mitochondrial bioenergetics of healthy mother-newborn dyads with varying degrees of CM.
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http://dx.doi.org/10.1073/pnas.2005885117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547248PMC
October 2020

Correction: Depression, mitochondrial bioenergetics, and electroconvulsive therapy: a new approach towards personalized medicine in psychiatric treatment - a short review and current perspective.

Transl Psychiatry 2020 08 10;10(1):277. Epub 2020 Aug 10.

Clinic for Psychiatry and Psychotherapy III, Ulm University Clinic, Ulm, Baden-Wuerttemberg, Germany.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41398-020-00973-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417589PMC
August 2020

Depression, mitochondrial bioenergetics, and electroconvulsive therapy: a new approach towards personalized medicine in psychiatric treatment - a short review and current perspective.

Transl Psychiatry 2020 07 9;10(1):226. Epub 2020 Jul 9.

Clinic for Psychiatry and Psychotherapy III, Ulm University Clinic, Ulm, Baden-Wuerttemberg, Germany.

Major depressive disorder (MDD) is a globally occurring phenomenon and developed into a severe socio-economic challenge. Despite decades of research, the underlying pathophysiological processes of MDD remain incompletely resolved. Like other mental disorders, MDD is hypothesized to mainly affect the central nervous system (CNS). An increasing body of research indicates MDD to also change somatic functioning, which impairs the physiological performance of the whole organism. As a consequence, a paradigm shift seems reasonable towards a systemic view of how MDD affects the body. The same applies to treatment strategies, which mainly focus on the CNS. One new approach highlights changes in the bioenergetic supply and intracellular network dynamics of mitochondria for the pathophysiological understanding of MDD. Mitochondria, organelles of mostly all eukaryotic cells, use carbon compounds to provide biochemical energy in terms of adenosine triphosphate (ATP). ATP is the bioenergetic currency and the main driver for enzymatic activity in all cells and tissues. Clinical symptoms of MDD including fatigue, difficulties concentrating, and lack of motivation were reported to be associated with impaired mitochondrial ATP production and changes in the density of the mitochondrial network. Additionally, the severity of these symptoms correlates negatively with mitochondrial functioning. Psychotherapy, antidepressant medication, and electroconvulsive therapy (ECT), a method used to treat severe and treatment-resistant forms of MDD, achieve robust antidepressant effects. The biological mechanisms beyond the treatment response to antidepressant strategies are partially understood. Here, mitochondrial functioning is discussed as a promising new biomarker for diagnosis and treatment effects in MDD.
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http://dx.doi.org/10.1038/s41398-020-00901-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347855PMC
July 2020

Effectiveness of a guided online mindfulness-focused intervention in a student population: Study protocol for a randomised control trial.

BMJ Open 2020 03 24;10(3):e032775. Epub 2020 Mar 24.

Department of Clinical & Health Psychology, Ulm University, Ulm, Baden-Württemberg, Germany.

Background: Previous studies show that university students experience higher psychological stress than the general population, resulting in increased vulnerability for mental disorders for the student population. Online mindfulness interventions will be delivered to students as a potentially promising and more flexible approach compared to face-to-face interventions with the aim of improving their mental health. This study purposes to investigate the effectiveness of a guided online mindfulness-focused intervention for university students by using both self-reported and psychobiological measures.

Methods And Analyses: In this multicentre, two-armed randomised controlled trial with a parallel design, a guided version of the online mindfulness-focused intervention 'StudiCare Mindfulness' will be compared with a waitlist control group. In total, 120 participants will be recruited at different universities (of Applied Sciences) in (Neu-) Ulm. Data will be assessed prior to randomisation, after eight weeks (post-intervention) and six months after randomisation (follow-up). The primary outcome measure is mindfulness. The secondary outcome measures include depression, anxiety and stress levels, well-being, interoceptive sensibility, emotion regulation and alexithymia. Psychobiological parameters comprise interoceptive accuracy, hair cortisol and FKBP5 genotype. Sociodemographic variables, treatment expectations, side and adverse side effects, as well as intervention satisfaction and adherence will be assessed. All data analyses will be conducted according to the intention-to-treat principle.

Ethics And Dissemination: All study procedures have been approved by the Ethics Committee of Ulm University (application No. 48/18). The findings will be disseminated widely through peer-reviewed publications and conference presentations.

Trial Registration Number: DRKS00014701.
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http://dx.doi.org/10.1136/bmjopen-2019-032775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202707PMC
March 2020

Childhood maltreatment compromises resilience against occupational trauma exposure: A retrospective study among emergency medical service personnel.

Child Abuse Negl 2020 01 13;99:104248. Epub 2019 Nov 13.

Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

Background: Childhood maltreatment (CM) compromises resilience against stress and trauma throughout life. Therefore, it could present a major risk factor for the health of frequently trauma-exposed professionals such as emergency medical service (EMS) personnel.

Objective: We investigated, whether EMS personnel's history of CM increased their risk for mental and physical stress symptoms after occupational trauma exposure.

Participants And Setting: Data from 103 German EMS personnel (age: Mdn±QD = 26.00 ± 8.50 years) were collected as part of a cross-sectional survey distributed among employees of the regional German Red Cross EMS division (response rate 46.6%). The sample corresponded well to the division's entire staff in terms of socio-anagraphic characteristics.

Methods: CM and occupational trauma exposure as well as posttraumatic, depressive, and somatic symptoms were assessed with self-report questionnaires.

Results: Moderation analyses indicated stronger positive associations between occupational trauma exposure and the severity of posttraumatic (β = .30, p < .001), depressive (β = .20, p = .026), and somatic symptoms (β = .18, p = .059) among EMS personnel who reported a higher exposure to CM.

Conclusions: Our study provides initial evidence that CM could increase the EMS personnel's vulnerability to the detrimental consequences of critical incidents on duty. Future research is needed (i) to replicate and generalize our observation on various trauma-exposed professions as well as (ii) to develop preventive measures for targeting the mediating and protective factors which influence the relationship between CM and the negative consequences of occupational trauma exposure.
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http://dx.doi.org/10.1016/j.chiabu.2019.104248DOI Listing
January 2020

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach.

Sci Rep 2019 04 18;9(1):983. Epub 2019 Apr 18.

Department of Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Albert-Einstein-Allee 47, Ulm, 89081, Germany.

While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CM-associated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation.
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http://dx.doi.org/10.1038/s41598-018-36689-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052131PMC
April 2019

The Association of Childhood Maltreatment With Lipid Peroxidation and DNA Damage in Postpartum Women.

Front Psychiatry 2019 18;10:23. Epub 2019 Feb 18.

Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic disorders in later life. A potential link could be oxidative stress, which is defined as the imbalance between the amount of reactive oxygen species (ROS) and the neutralizing capacity of anti-oxidative defense systems. However, the findings linking CM with oxidative stress have been inconsistent so far. In this study, we aimed to further explore this association by investigating biological markers of DNA and lipid damage due to oxidation in a comprehensive approach over two study cohorts of postpartum women (study cohort I and study cohort II). The severity of CM experiences (maltreatment load) was assessed in both studies using the . In study cohort I ( = 30), we investigated whether CM was associated with higher levels of structural DNA damage in peripheral blood mononuclear cells (PBMC) by two methods that are highly sensitive for detecting nuclear DNA strand breaks (comet assay and γH2AX staining). In study cohort II ( = 117), we then assessed in a larger cohort, that was specifically controlled for potential confounders for oxidative stress measurements, two established serum and plasma biomarkers of oxidative stress, one representing oxidative DNA and RNA damage (8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine; 8-OH(d)G) and the other representing lipid peroxidation (8-isoprostane). In study cohort I, the analyses revealed no significant main effects of maltreatment load on cellular measures of nuclear DNA damage. The analyses of peripheral oxidative stress biomarkers in study cohort II revealed a significant main effect of maltreatment load on free 8-isoprostane plasma levels, but not on total 8-isprostane plasma levels and 8-OH(d)G serum levels. Taken together, by combining different methods and two study cohorts, we found no indications for higher oxidative DNA damages with higher maltreatment load in postpartum women. Further research is needed to investigate whether this increase in free 8-isoprostane is a marker for oxidative stress or whether it is instead functionally involved in ROS-related signaling pathways that potentially regulate inflammatory processes following a history of CM.
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http://dx.doi.org/10.3389/fpsyt.2019.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387959PMC
February 2019

Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts.

Psychophysiology 2020 01 17;57(1):e13288. Epub 2018 Oct 17.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

The risk of developing posttraumatic stress disorder (PTSD) increases with the number of traumatic event types experienced (trauma load) in interaction with other psychobiological risk factors. The NOTCH (neurogenic locus notch homolog proteins) signaling pathway, consisting of four different trans-membrane receptor proteins (NOTCH1-4), constitutes an evolutionarily well-conserved intercellular communication pathway (involved, e.g., in cell-cell interaction, inflammatory signaling, and learning processes). Its association with fear memory consolidation makes it an interesting candidate for PTSD research. We tested for significant associations of common genetic variants of NOTCH1-4 (investigated by microarray) and genomic methylation of saliva-derived DNA with lifetime PTSD risk in independent cohorts from Northern Uganda (N = 924) and Rwanda (N = 371), and investigated whether NOTCH-related gene sets were enriched for associations with lifetime PTSD risk. We found associations of lifetime PTSD risk with single nucleotide polymorphism (SNP) rs2074621 (NOTCH3) (p = 0.04) in both cohorts, and with methylation of CpG site cg17519949 (NOTCH3) (p = 0.05) in Rwandans. Yet, none of the (epi-)genetic associations survived multiple testing correction. Gene set enrichment analyses revealed enrichment for associations of two NOTCH pathways with lifetime PTSD risk in Ugandans: NOTCH binding (p = 0.003) and NOTCH receptor processing (p = 0.01). The environmental factor trauma load was significant in all analyses (all p < 0.001). Our integrated methodological approach suggests NOTCH as a possible mediator of PTSD risk after trauma. The results require replication, and the precise underlying pathophysiological mechanisms should be illuminated in future studies.
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http://dx.doi.org/10.1111/psyp.13288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379258PMC
January 2020

Targeting the association between telomere length and immuno-cellular bioenergetics in female patients with Major Depressive Disorder.

Sci Rep 2018 06 20;8(1):9419. Epub 2018 Jun 20.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

Major Depressive Disorder (MDD) has been associated with telomere dysfunction and alterations in mitochondrial activity, which seem to be co-regulated in human cells. To investigate this co-regulation in MDD, we assessed telomere length (TL) in peripheral blood mononuclear cells (PBMC) and selected immune cell subsets by quantitative fluorescence in situ hybridization and mitochondrial respiratory activity in PBMC by high-resolution respirometry in a study cohort of 18 MDD patients and 21 non-depressed controls. We provide initial evidence for a differential vulnerability to telomere attrition in selected adaptive immune cell populations. Here we found the highest difference in TL between depressed and control subjects for memory cytotoxic T cells. Depression was associated with reduced mitochondrial activity (mitochondrial bioenergetics), but increased mitochondrial density (mitochondrial biogenesis) in PBMC. Exploratory post-hoc analyses indicated that the changes in TL and immune cell bioenergetics were most pronounced in MDD patients who reported experiences of childhood sexual abuse. Among MDD patients, PBMC TL was as a trend positively associated with mitochondrial density and negatively associated with mitochondrial leak respiration, but not with mitochondrial activity related to biological energy production. These initial findings support the hypothesis of a co-regulation between telomeres and mitochondrial biogenesis but not mitochondrial bioenergetics among MDD patients.
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http://dx.doi.org/10.1038/s41598-018-26867-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010455PMC
June 2018

The association between cortisol, oxytocin, and immune cell mitochondrial oxygen consumption in postpartum women with childhood maltreatment.

Psychoneuroendocrinology 2018 10 1;96:69-77. Epub 2018 Jun 1.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Albert-Einstein-Allee 47, 89081, Ulm, Germany.

Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic diseases in later life. Individual risk and resilience factors may, however, influence how deep psychological stress gets under the skin. We hypothesized that the stress-related hormone cortisol and the attachment-related hormone oxytocin constitute biological factors that might moderate the biological sequelae and long-term health outcomes associated with CM. As biological outcome, we thereby focused on immunocellular oxygen consumption, which we previously found to be increased with a higher severity of CM experiences. In a study cohort of N = 49 postpartum women, we investigated the interaction between CM experiences, serum cortisol and plasma oxytocin levels, and the cellular oxygen consumption of intact peripheral blood mononuclear cells (PBMC) by high-resolution respirometry. Regression analyses revealed a significant interaction between the severity of CM experiences and cortisol as well as oxytocin on cellular oxygen consumption of PBMC three months postpartum: higher cortisol levels were thereby associated with an increase in oxygen consumption related to basal mitochondrial respiration and ATP turnover, while oxygen consumption related to basal mitochondrial respiration and ATP turnover were reduced with higher oxytocin levels in individuals with higher CM severity. These associations were not seen among women with no or low CM experiences. Together, the results suggest that cortisol and oxytocin might be associated with opposite effects on CM-related alterations in the bioenergetic profile of peripheral immune cells.
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http://dx.doi.org/10.1016/j.psyneuen.2018.05.040DOI Listing
October 2018

Intergenerational gene × environment interaction of FKBP5 and childhood maltreatment on hair steroids.

Psychoneuroendocrinology 2018 06 5;92:103-112. Epub 2018 Apr 5.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany. Electronic address:

Background: The inconsistency in results of cortisol alterations after childhood maltreatment (CM) might arise due to the fact that no study so far considered the effects of environmental factors such as maltreatment load and genetic factors such as the influence of FKBP5 genotype on stress hormone regulation. This study analyzed the interaction between the single nucleotide polymorphism rs1360780 within the FKBP5 gene and the severity of maternal CM experiences (maltreatment load) on hair steroid levels of mother-infant-dyads.

Methods: Hair samples of N = 474 mothers and N = 331 newborns were collected < 1 week after parturition enabling a retrospective assessment of cortisol, cortisone, and dehydroepiandrosterone (DHEA) using mass spectrometry. The sum score of the Childhood Trauma Questionnaire operationalized the maternal maltreatment load. DNA from whole blood or buccal cells was used for FKBP5 genotyping.

Results: The higher the maltreatment load, the higher maternal hair cortisol and cortisone levels in T allele carriers of FKBP5 rs1360780 were observed. Hair cortisol and DHEA levels of newborns with the T allele were reduced with an increasing maternal maltreatment load, while there was an increase of hair cortisol and DHEA in newborns homozygous for the C allele.

Conclusions: This study is the very first uncovering a gene (FKBP5) × environment (maltreatment load) interaction on hair steroids in mothers and their offspring, indicating an intergenerational transmission of hypothalamic-pituitary-adrenal axis alterations. These results may help to explain the inconsistency in previous findings on steroid hormone alterations after chronic and traumatic stress and should be considered in future studies.
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http://dx.doi.org/10.1016/j.psyneuen.2018.04.002DOI Listing
June 2018

Altered hair endocannabinoid levels in mothers with childhood maltreatment and their newborns.

Biol Psychol 2018 05 19;135:93-101. Epub 2018 Mar 19.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany. Electronic address:

The endocannabinoid (EC) system possesses anti-inflammatory properties and seems to be altered in trauma-exposed individuals. In an intergenerational approach, this study investigated the link between childhood maltreatment (CM) experiences and alterations in the EC system. Hair samples of N = 142 mothers and N = 91 newborns were analyzed, retrospectively assessing EC regulation during the last trimester of pregnancy with four ECs: 1-arachidonoylglycerol (1-AG), N-oleoylethanolamide (OEA), N-stearoylethanolamide (SEA), and N-palmitoylethanolamide (PEA). Compared to mothers without CM, hair of mothers with CM showed significantly higher levels of 1-AG and lower levels of SEA. Newborns of mothers with CM exhibited higher levels of 1-AG and OEA. Furthermore, the higher the severity of maternal CM, the lower were maternal SEA levels and the higher neonatal OEA levels. Findings indicate altered EC levels during the last trimester of pregnancy in mothers with CM and their developing fetus, highlighting potential intergenerational effects from one generation to the other.
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http://dx.doi.org/10.1016/j.biopsycho.2018.03.006DOI Listing
May 2018

Child Maltreatment Is Associated with a Reduction of the Oxytocin Receptor in Peripheral Blood Mononuclear Cells.

Front Psychol 2018 27;9:173. Epub 2018 Feb 27.

Department of Psychosomatic Medicine and Psychotherapy, Ulm University, Ulm, Germany.

Child maltreatment (CM) and attachment experiences are closely linked to alterations in the human oxytocin (OXT) system. However, human data about oxytocin receptor (OXTR) protein levels are lacking. Therefore, we investigated oxytocin receptor (OXTR) protein levels in circulating immune cells and related them to circulating levels of OXT in peripheral blood. We hypothesized reduced OXTR protein levels, associated with both, experiences of CM and an insecure attachment representation. OXTR protein expressions were analyzed by western blot analyses in peripheral blood mononuclear cells (PBMC) and plasma OXT levels were determined by radioimmunoassay (RIA) in 49 mothers. We used the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Attachment representations (secure vs. insecure) were classified using the Adult Attachment Projective Picture System (AAP) and levels of anxiety and depression were assessed with the German version of the Hospital Depression and Anxiety scale (HADS-D). CM-affected women showed significantly lower OXTR protein expression with significantly negative correlations between the OXTR protein expression and the CTQ sum score, whereas plasma OXT levels showed no significant differences in association with CM. Lower OXTR protein expression in PBMC were particularly pronounced in the group of insecurely attached mothers compared to the securely attached group. Anxiety levels were significantly higher in CM-affected women. This study demonstrated a significant association between CM and an alteration of OXTR protein expression in human blood cells as a sign for chronic, long-lasting alterations in this attachment-related neurobiological system.
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http://dx.doi.org/10.3389/fpsyg.2018.00173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835067PMC
February 2018

Alterations of the serum N-glycan profile in female patients with Major Depressive Disorder.

J Affect Disord 2018 07 27;234:139-147. Epub 2018 Feb 27.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

Background: 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.

Methods: 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.

Results: 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.

Limitations: The relatively small sample size and the presence of potential confounders (e.g., BMI, smoking, medication).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.jad.2018.02.082DOI Listing
July 2018

Serum profile changes in postpartum women with a history of childhood maltreatment: a combined metabolite and lipid fingerprinting study.

Sci Rep 2018 02 22;8(1):3468. Epub 2018 Feb 22.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Albert-Einstein-Allee 47, 89081, Ulm, Germany.

Childhood maltreatment (CM) can increase the risk of adverse health consequences in adulthood. A deeper insight in underlying biological pathways would be of high clinical relevance for early detection and intervention. The untargeted investigation of all detectable metabolites and lipids in biological samples represents a promising new avenue to identify so far unknown biological pathways associated with CM. Using an untargeted approach, liquid chromatography-mass spectrometry (LC-MS) was performed on peripheral blood serum samples collected three months postpartum from 105 women with varying degrees of CM exposure. Comprehensive univariate and multivariate statistical analyses consistently identified eight biomarker candidates putatively belonging to antioxidant-, lipid-, and endocannabinoid-associated pathways, which differentiated between women with and without CM. Classification algorithms allowed for clear prediction of the CM status with high accuracy scores (~80-90%). Similar results were obtained when excluding all women with a lifetime psychiatric diagnosis. In order to confirm the identities of these promising biomarker candidates, LC-MS/MS analysis was applied, confirming one of the metabolites as bilirubin IXa, a potent antioxidant with immunomodulatory properties. In sum, our results suggest novel pathways that could explain long-term effects of CM on health and disease by influencing biological patterns associated with energy metabolism, inflammation, and oxidative stress.
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http://dx.doi.org/10.1038/s41598-018-21763-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823924PMC
February 2018

History of child maltreatment and telomere length in immune cell subsets: Associations with stress- and attachment-related hormones.

Dev Psychopathol 2018 05 14;30(2):539-551. Epub 2017 Aug 14.

Ulm University.

Experiencing maltreatment during childhood can have long-lasting consequences for both mental and physical health. Immune cell telomere length (TL) shortening might be one link between child maltreatment (CM) experiences and adverse health outcomes later in life. While the stress hormone cortisol has been associated with TL attrition, the attachment-related hormone oxytocin may promote resilience. In 15 mothers with and 15 age- and body mass index-matched mothers without CM, we assessed TL in peripheral blood mononuclear cells and selected immune cell subsets (monocytes, naive, and memory cytotoxic T cells) by quantitative fluorescence in situ hybridization, as well as peripheral cortisol and oxytocin levels. Memory cytotoxic T cells showed significantly shorter TL in association with CM, whereas TL in monocytes and naive cytotoxic T cells did not significantly differ between the two groups. Across both groups, cortisol was negatively associated with TL, while oxytocin was positively associated with TL in memory cytotoxic T cells. These results indicate that long-lived memory cytotoxic T cells are most affected by the increased biological stress state associated with CM. Keeping in mind the correlational and preliminary nature of the results, the data suggest that cortisol may have a damaging and oxytocin a protective function on TL.
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http://dx.doi.org/10.1017/S0954579417001055DOI Listing
May 2018

Novel Blood-Based Biomarkers of Cognition, Stress, and Physical or Cognitive Training in Older Adults at Risk of Dementia: Preliminary Evidence for a Role of BDNF, Irisin, and the Kynurenine Pathway.

J Alzheimers Dis 2017 ;59(3):1097-1111

Department of Neurology, Ulm University, Germany.

 Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.
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http://dx.doi.org/10.3233/JAD-170447DOI Listing
April 2018

Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers.

Front Hum Neurosci 2016 8;10:627. Epub 2016 Dec 8.

Institute of Psychology, University of Innsbruck Innsbruck, Austria.

Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the "hormone of affiliation" and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants ( = 0.004) and cortisol decreased in the significant majority of 73% participants ( = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as well as males and include a control stimulus condition.
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http://dx.doi.org/10.3389/fnhum.2016.00627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143683PMC
December 2016

Inflammation in adult women with a history of child maltreatment: The involvement of mitochondrial alterations and oxidative stress.

Mitochondrion 2016 09 13;30:197-207. Epub 2016 Aug 13.

Clinical & Biological Psychology, Institute of Psychology and Education, Ulm University, Albert-Einstein-Allee 47, 89081 Ulm, Germany.

The experience of maltreatment during childhood is associated with chronic low-grade inflammation in adulthood. However, the molecular mechanisms underlying this pro-inflammatory phenotype remain unclear. Mitochondria were recently found to principally coordinate inflammatory processes via both inflammasome activation and inflammasome-independent pathways. To this end, we hypothesized that alterations in immune cell mitochondrial functioning and oxidative stress might be at the interface between the association of maltreatment experiences during childhood and inflammation. We analyzed pro-inflammatory biomarkers (levels of C-reactive protein, cytokine secretion by peripheral blood mononuclear cells (PBMC) in vitro, PBMC composition, lysophosphatidylcholine levels), serum oxidative stress levels (arginine:citrulline ratio, l-carnitine and acetylcarnitine levels) and mitochondrial functioning (respiratory activity and density of mitochondria in PBMC) in peripheral blood samples collected from 30 women (aged 22-44years) with varying degrees of maltreatment experiences in form of abuse and neglect during childhood. Exposure to maltreatment during childhood was associated with an increased ROS production, higher levels of oxidative stress and an increased mitochondrial activity in a dose-response relationship. Moreover, the increase in mitochondrial activity and ROS production were positively associated with the release of pro-inflammatory cytokines by PBMC. Decreased serum levels of lysophosphatidylcholines suggested higher inflammasome activation with increasing severity of child maltreatment experiences. Together these findings offer preliminary evidence for the association of alterations in immune cell mitochondrial functioning, oxidative stress and the pro-inflammatory phenotype observed in individuals with a history of maltreatment during childhood. The results emphasize that the early prevention of child abuse and neglect warrants more attention, as the experience of maltreatment during childhood might have life-long consequences for physical health.
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http://dx.doi.org/10.1016/j.mito.2016.08.006DOI Listing
September 2016

Telomere shortening leads to earlier age of onset in ALS mice.

Aging (Albany NY) 2016 Feb;8(2):382-93

Department of Neurology, Ulm University, 89081 Ulm, Germany.

Telomere shortening has been linked to a variety of neurodegenerative diseases. Recent evidence suggests that reduced telomerase expression results in shorter telomeres in leukocytes from sporadic patients with amyotrophic lateral sclerosis (ALS) compared with healthy controls. Here, we have characterized telomere length in microglia, astroglia and neurons in human post mortem brain tissue from ALS patients and healthy controls. Moreover, we studied the consequences of telomerase deletion in a genetic mouse model for ALS. We found a trend towards longer telomeres in microglia in the brains of ALS patients compared to non-neurologic controls. Knockout of telomerase leading to telomere shortening accelerated the ALS phenotype inSOD1G93A-transgenic mice. Our results suggest that telomerase dysfunction might contribute to the age-related risk for ALS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789589PMC
http://dx.doi.org/10.18632/aging.100904DOI Listing
February 2016

Endocannabinoid concentrations in hair are associated with PTSD symptom severity.

Psychoneuroendocrinology 2016 May 12;67:198-206. Epub 2016 Feb 12.

Clinical & Biological Psychology, Institute of Psychology & Education, Ulm University, Albert-Einstein-Allee 47, 89069 Ulm, Germany.

The endocannabinoid system has been implicated in the regulation of the stress response, fear memory formation, and inflammatory processes. Posttraumatic stress disorder (PTSD) can result from exposure to extreme stress and is characterized by strong, associative memories for the traumatic events experienced. Furthermore, an elevated physical disease risk has been observed in PTSD, likely to be mediated by inflammatory processes. Therefore, altered endocannabinoid regulation can be expected in individuals with PTSD. However, attempts to assess PTSD-associated differences in the endocannabinoid system from human blood samples have provided inconsistent results, possibly due to fluctuating levels of endocannabinoids. In hair, these neuromodulators are accumulated over time and thus give access to a more stable and reliable assessment. We therefore investigated PTSD-associated differences in hair concentrations of endocannabinoids (N-acyl-ethanolamides palmitoylethanolamide [PEA], oleoylethanolamide [OEA] and stearoylethanolamide [SEA]) in 38 rebel war survivors from Northern Uganda suffering from PTSD and N=38 healthy rebel war survivors without current and lifetime PTSD. PTSD diagnosis and symptom severity were assessed in structured clinical interviews employing the Posttraumatic Diagnostic Scale (PDS). A significant group difference was observed for OEA, with PTSD patients showing reduced hair concentrations. Regression analyses further revealed strong negative relationships between all investigated N-acyl-ethanolamides and symptom severity of PTSD. The observed reductions in endocannabinoids might account for the increased inflammatory state as well as for the failure to extinguish fear memories observed in PTSD. Our findings add to the accumulating evidence suggesting the endocannabinoid system as a target for pharmacological enhancement of exposure-based psychotherapy for PTSD.
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http://dx.doi.org/10.1016/j.psyneuen.2016.02.010DOI Listing
May 2016

Metabolite profiling in posttraumatic stress disorder.

J Mol Psychiatry 2015 8;3(1). Epub 2015 Feb 8.

Clinical & Biological Psychology, Ulm University, Albert-Einstein Allee 47, 89081 Ulm, Germany.

Background: Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes. Despite increasing efforts, we only begin to understand the underlying biomolecular processes. The hypothesis-free assessment of a wide range of metabolites (termed metabolite profiling) might contribute to the discovery of biological pathways underlying PTSD.

Methods: Here, we present the results of the first metabolite profiling study in PTSD, which investigated peripheral blood serum samples of 20 PTSD patients and 18 controls. We performed liquid chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass spectrometry. Two complementary statistical approaches were used to identify metabolites associated with PTSD status including univariate analyses and Partial Least Squares Discriminant Analysis (PLS-DA).

Results: Thirteen metabolites displayed significant changes in PTSD, including four glycerophospholipids, and one metabolite involved in endocannabinoid signaling. A biomarker panel of 19 metabolites classifies PTSD with 85% accuracy, while classification accuracy from the glycerophospholipid with the highest differentiating ability already reached 82%.

Conclusions: This study illustrates the feasibility and utility of metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid signaling as potential biological pathways involved in trauma-associated pathophysiology.
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http://dx.doi.org/10.1186/s40303-015-0007-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367823PMC
April 2015

Telomere shortening in leukocyte subpopulations in depression.

BMC Psychiatry 2014 Jul 5;14:192. Epub 2014 Jul 5.

Clinical & Biological Psychology, Institute of Psychology and Education, University of Ulm, Ulm, Germany.

Background: Telomere shortening is a normal age-related process. However, premature shortening of telomeres in leukocytes--as has been reported in depression--may increase the risk for age-related diseases. While previous studies investigated telomere length in peripheral blood mononuclear cells (PBMCs) as a whole, this study investigated specific changes in the clonal composition of white blood cells of the adaptive immune system (CD4+ helper and CD8+ cytotoxic T lymphocytes, and CD20+ B lymphocytes).

Methods: Forty-four females with a history of unipolar depression were investigated and compared to fifty age-matched female controls. Telomere lengths were compared between three groups: 1) individuals with a history of depression but currently no clinically relevant depressive symptoms, 2) individuals with a history of depression with relevant symptoms of depression, and 3) healthy age-matched controls. Telomere length was assessed using quantitative fluorescence in situ hybridization (qFISH).

Results: Both groups with a history of unipolar depression (with and without current depressive symptoms) showed significantly shorter telomeres in all three lymphocyte subpopulations. The effect was stronger in CD8+ and CD20+ cells than in CD4+ cells. Individuals with a history of depression and with (without) current symptoms exhibited a CD8+ telomere length shortening corresponding to an age differential of 27.9 (25.3) years.

Conclusions: A history of depression is associated with shortened telomeres in the main effector populations of the adaptive immune system. Shorter telomeres seem to persist in individuals with lifetime depression independently of the severity of depressive symptoms. CD8+ cytotoxic T cells and CD20+ B cells seem to be particularly affected in depression. The total number of depressive episodes did not influence telomere length in the investigated adaptive immune cell populations.
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http://dx.doi.org/10.1186/1471-244X-14-192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098691PMC
July 2014

Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder.

PLoS One 2013 7;8(5):e62741. Epub 2013 May 7.

Department of Anaesthesiology, Ludwig-Maximilians-University, Munich, Germany.

Background: Endocannabinoids (ECs) and related N-acyl-ethanolamides (NAEs) play important roles in stress response regulation, anxiety and traumatic memories. In view of the evidence that circulating EC levels are elevated under acute mild stressful conditions in humans, we hypothesized that individuals with traumatic stress exposure and post-traumatic stress disorder (PTSD), an anxiety disorder characterized by the inappropriate persistence and uncontrolled retrieval of traumatic memories, show measurable alterations in plasma EC and NAE concentrations.

Methods: We determined plasma concentrations of the ECs anandamide (ANA) and 2-arachidonoylglycerol (2-AG) and the NAEs palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamine (SEA), and N-oleoyldopamine (OLDA) by HPLC-MS-MS in patients with PTSD (n = 10), trauma-exposed individuals without evidence of PTSD (n = 9) and in healthy control subjects (n = 29). PTSD was diagnosed according to DSM-IV criteria by administering the Clinician Administered PTSD Scale (CAPS), which also assesses traumatic events.

Results: Individuals with PTSD showed significantly higher plasma concentrations of ANA (0.48 ± 0.11 vs. 0.36 ± 0.14 ng/ml, p = 0.01), 2-AG (8.93 ± 3.20 vs. 6.26±2.10 ng/ml, p<0.01), OEA (5.90 ± 2.10 vs. 3.88 ± 1.85 ng/ml, p<0.01), SEA (2.70 ± 3.37 vs. 0.83 ± 0.47, ng/ml, p<0.05) and significantly lower plasma levels of OLDA (0.12 ± 0.05 vs. 0.45 ± 0.59 ng/ml, p<0.05) than healthy controls. Moreover, PTSD patients had higher 2-AG plasma levels (8.93 ± 3.20 vs. 6.01 ± 1.32 ng/ml, p = 0.03) and also higher plasma concentrations of PEA (4.06 ± 1.87 vs. 2.63±1.34 ng/ml, p<0.05) than trauma-exposed individuals without evidence of PTSD. CAPS scores in trauma-exposed individuals with and without PTSD (n = 19) correlated positively with PEA (r = 0.55, p = 0.02) and negatively with OLDA plasma levels (r = -0.68, p<0.01). CAPS subscores for intrusions (r = -0.65, p<0.01), avoidance (r = -0.60, p<0.01) and hyperarousal (r = -0.66, p<0.01) were all negatively related to OLDA plasma concentrations.

Conclusions: PTSD appears to be associated with changes in plasma EC/NAE concentrations. This may have pathophysiological and diagnostic consequences but will need to be reproduced in larger cohorts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062741PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647054PMC
December 2013
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