Publications by authors named "Nicolas Rohleder"

102 Publications

Associations of working conditions and chronic low-grade inflammation among employees: a systematic review and meta-analysis.

Scand J Work Environ Health 2021 Sep 15. Epub 2021 Sep 15.

Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Ziemssenstraße 1, 80336, München, Germany.

Objectives Chronic low-grade inflammation has been identified as a key pathway linking stress experience to human health. However, systematic evaluations on the relationship of work stress and immune function are scarce and predominantly based on cross-sectional studies. We performed a systematic review and meta-analysis of prospective studies on associations of working conditions and inflammatory biomarkers. Methods In line with our previously established study protocol and the PRISMA-guidelines, we systematically searched electronic databases for prospective studies on working conditions as well as workplace interventions and inflammatory markers in employees. We classified studies (by design, type of exposure/intervention, outcome) and performed rigorous risk-of-bias assessments. Studies were summarized qualitatively, and a meta-analysis was conducted. Results We identified 23 eligible studies (N=16 432) with a broad scope of working conditions and inflammatory markers. For interventional designs, we differentiated between individual-directed/behavioral (including physical and mental) and organization-directed/structural interventions. Workplace physical exercise interventions were associated with a decrease in C-reactive protein (k=5; d=-0.61; P<0.001). For other workplace interventions, ie, mental and organizational/structural, results were inconclusive. Concerning observational studies, dimensions of the job demand-control(-support) model were most frequently investigated, and results showed weak - if any - associations with inflammatory markers. Conclusions The research base was heterogeneous and high-level evidence was limited. More prospective studies are needed with broader consideration of work stressors and inflammatory markers. For practical occupational health management, exercise interventions are effective measures to reduce chronic low-grade inflammation.
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http://dx.doi.org/10.5271/sjweh.3982DOI Listing
September 2021

Physiological stress in safer cycling in older age (SiFAr-stress): effect of a multicomponent exercise intervention-a study protocol for a randomized controlled trial.

Trials 2021 Aug 21;22(1):552. Epub 2021 Aug 21.

Department of Psychology, Chair of Health Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Bavaria, Germany.

Background: SiFAr-Stress investigates the impact of cycling on stress levels in older adults. Uncertainty due to change to motorized bicycle or fear of falling can be perceived as stressors for cyclists. Stress activates different physiological signal cascades and stimulates the hypothalamic-pituitary-adrenal (HPA) axis, which leads to the release of the stress hormone cortisol and further effects such as the development of low-grade inflammation. Both can-in the long term-be associated with negative health outcomes. The aim of the study SiFAr-Stress is to analyze inflammatory processes as well as the activity of stress systems before and after a cycling intervention for older adults.

Methods: In this study, community-dwelling older adults aged 65 years and older will be randomly assigned to either a cycling or a control intervention in a parallel-group design. Objective HPA axis-related measures (saliva cortisol and hair cortisol) will be assessed before, after, and 6-9 months after the cycling and control intervention (T0, T1, and T2). Furthermore, changes in cortisol reactivity in response to the cycling intervention will be investigated at the second and seventh training lessons. Furthermore, secondary outcomes (fear of falling, perceived stress, salivary alpha amylase, and C-reactive protein) will be assessed at T0, T1, and T2.

Discussion: The study will be the first, in which stress- and health-related bio-physiological outcomes will be assessed in the context of a multicomponent exercise intervention, addressing cycling in older adults. It will enable us to better understand the underlying patho-physiological and psychological mechanisms and will help to improve interventions for this target group.

Trial Registration: ClinicalTrials.gov NCT04362514 . Prospectively registered on 27 April 2020.
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http://dx.doi.org/10.1186/s13063-021-05481-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379566PMC
August 2021

Association of Prenatal Alcohol Exposure and Prenatal Maternal Depression with Offspring Low-Grade Inflammation in Early Adolescence.

Int J Environ Res Public Health 2021 07 27;18(15). Epub 2021 Jul 27.

Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.

(1) This longitudinal study aimed to investigate the link between prenatal alcohol exposure and prenatal maternal depression with the offspring's low-grade inflammatory status. (2) Prenatal alcohol exposure was determined via maternal self-report during the 3rd trimester of pregnancy (self-report+: = 29) and the meconium alcohol metabolite Ethyl Glucuronide (EtG), collected at birth (≥30 ng/g: = 23). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for prenatal maternal depressive symptoms during the 3rd trimester (≥10: = 35). Fifteen years later, 122 adolescents ( = 13.32 years; 48.4% female) provided blood samples for the analysis of high sensitivity C-reactive protein (hsCRP; = 0.91; = 1.28). (3) Higher hsCRP levels were found in EtG positive adolescents ( = 0.036, ηp = 0.04) and an inverse non-significant dose-response relation with hsCRP ( = -0.35, = 0.113). For maternal self-reported prenatal alcohol consumption ( = 0.780, ηp = 0.00) and prenatal depressive symptoms ( = 0.360, ηp = 0.01) no differences for hsCRP levels between the affected and unaffected groups were found. (4) Adolescents with prenatal alcohol exposure are at risk for low-grade systemic inflammation. The EtG biomarker may be more accurate compared to self-reports. The findings suggest that prenatal maternal depression does not evoke low-grade systemic inflammation.
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http://dx.doi.org/10.3390/ijerph18157920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345560PMC
July 2021

Associations Between C-Reactive Protein Levels, Exercise Addiction, and Athlete Burnout in Endurance Athletes.

Front Psychol 2021 4;12:615715. Epub 2021 Jun 4.

Chair of Health Psychology, Department of Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Regular physical activity can support long-term health maintenance, e.g., by reducing inflammatory markers such as C-reactive protein (CRP) levels. However, excessive physical activity can promote the development of both mental and physical illness as well. From a psychological perspective, excessive exercise can lead to the development of exercise addiction (EA) and athlete burnout (AB). However, EA and AB have been rarely investigated so far and it is still unknown whether they are associated with risk factors for physical diseases such as increased CRP levels. In our study, we investigated whether EA and AB in endurance athletes are associated with CRP concentrations. Furthermore, sex differences and prevalence rates of EA were investigated. Ninety-five endurance athletes participated (54.7% female, mean age = 31.8 ± 15.02 years). CRP levels were assessed by means of Dried Blood Spots. For EA and AB assessment, the Exercise Addiction Inventory (EAI) and the Athlete Burnout Questionnaire (ABQ) were used. Exercise addiction was negatively associated with CRP in men. No associations were found for women. None of the ABQ subscales (physical and emotional exhaustion, devaluation of sports, and reduced sense of accomplishment) was associated with CRP levels or with EA. Prevalence of EA was 4.2%. More than 80% of the participants were at risk for EA development. Our results suggest that EA is not necessarily associated with a higher risk for physical diseases through inflammatory pathways. However, EA is a serious mental illness that is widespread in athletes, at least at a subclinical level.
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http://dx.doi.org/10.3389/fpsyg.2021.615715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211739PMC
June 2021

Clinical Ecopsychology: The Mental Health Impacts and Underlying Pathways of the Climate and Environmental Crisis.

Front Psychiatry 2021 21;12:675936. Epub 2021 May 21.

Psychopathology and Clinical Intervention, Institute of Psychology, University of Zürich, Zurich, Switzerland.

Humankind is confronted with progressing climate change, pollution, environmental degradation, and/or destruction of the air, soil, water, and ecosystems. The climate and environmental crisis is probably one of the greatest challenges in the history of humankind. It not only poses a serious current and continuing threat to physical health, but is also an existing and growing hazard to the mental health of millions of people worldwide. This synergy of literature provides a current summary of the adverse mental health impacts of the climate and environmental crisis from the perspective of Clinical Psychology. Furthermore, it presents potential underlying processes, including biological, emotional, cognitive, behavioral, and social pathways. The existing data suggest that the climate and environmental crisis not only acts as a direct stressor, but can also exert a detrimental impact on the various pathways, with the potential to amplify an individual's biopsychosocial vulnerability to develop mental ill-health. This is a call for an increased investigation into this emerging research field of Clinical Ecopsychology by clinical psychologists and other researchers.
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http://dx.doi.org/10.3389/fpsyt.2021.675936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175799PMC
May 2021

Interleukin-6 secretion upon acute psychosocial stress as a potential predictor of psychotherapy outcome in posttraumatic stress disorder.

J Neural Transm (Vienna) 2021 Sep 14;128(9):1301-1310. Epub 2021 May 14.

Department of Psychosomatic Medicine and Psychotherapy, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 4, 91054, Erlangen, Germany.

Posttraumatic stress disorder (PTSD) is a severe mental disorder that can develop after a traumatic event. PTSD has been reported to be associated with activation of the innate immune system, as measured by increased levels of pro-inflammatory cytokines. While it is well known that PTSD patients display increased levels of interleukin 6 (IL-6) when compared with healthy controls, the relationship between cytokine secretion and treatment outcome has been hardly investigated yet. The aim of this study was to assess the potential association of inflammatory activation and therapy outcome in PTSD. Before therapeutic intervention, we applied the Trier Social Stress Test (TSST) as a method to elicit psychosocial stress and an acute inflammatory response. IL-6 levels were measured in blood plasma of PTSD patients at different time points before and after the TSST. Severity of depressive, trauma-related, and somatic symptoms was assessed before and 8 weeks after trauma-focused treatment in a multimodal day clinic setting. We showed that high reactivity of IL-6 to psychosocial stress at the beginning of the therapy was associated with a negative therapy outcome in PTSD, especially regarding depressive symptoms. This study suggests plasma IL-6 reactivity as a potential molecular marker to predict treatment outcome in PTSD.
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http://dx.doi.org/10.1007/s00702-021-02346-8DOI Listing
September 2021

Commentary: Connecting cytokines to distress via cortisol concentrations.

Brain Behav Immun 2021 07 6;95:21-22. Epub 2021 Apr 6.

Department of Psychiatry and Addiction, University of Montreal, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2021.03.027DOI Listing
July 2021

Contactless analysis of heart rate variability during cold pressor test using radar interferometry and bidirectional LSTM networks.

Sci Rep 2021 Feb 4;11(1):3025. Epub 2021 Feb 4.

Hamburg University of Technology, Institute of High-Frequency Technology, 21073, Hamburg, Germany.

Contactless measurement of heart rate variability (HRV), which reflects changes of the autonomic nervous system (ANS) and provides crucial information on the health status of a person, would provide great benefits for both patients and doctors during prevention and aftercare. However, gold standard devices to record the HRV, such as the electrocardiograph, have the common disadvantage that they need permanent skin contact with the patient. Being connected to a monitoring device by cable reduces the mobility, comfort, and compliance by patients. Here, we present a contactless approach using a 24 GHz Six-Port-based radar system and an LSTM network for radar heart sound segmentation. The best scores are obtained using a two-layer bidirectional LSTM architecture. To verify the performance of the proposed system not only in a static measurement scenario but also during a dynamic change of HRV parameters, a stimulation of the ANS through a cold pressor test is integrated in the study design. A total of 638 minutes of data is gathered from 25 test subjects and is analysed extensively. High F-scores of over 95% are achieved for heartbeat detection. HRV indices such as HF norm are extracted with relative errors around 5%. Our proposed approach is capable to perform contactless and convenient HRV monitoring and is therefore suitable for long-term recordings in clinical environments and home-care scenarios.
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http://dx.doi.org/10.1038/s41598-021-81101-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862409PMC
February 2021

Mitochondrial respiratory capacity modulates LPS-induced inflammatory signatures in human blood.

Brain Behav Immun Health 2020 May 6;5. Epub 2020 May 6.

Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, United States.

Mitochondria modulate inflammatory processes in various model organisms, but it is unclear how much mitochondria regulate immune responses in human blood leukocytes. Here, we examine the effect of i) experimental perturbations of mitochondrial respiratory chain function, and ii) baseline inter-individual variation in leukocyte mitochondrial energy production capacity on stimulated cytokine release and glucocorticoid (GC) sensitivity. In a first cohort, whole blood from 20 healthy women and men was stimulated with increasing concentrations of the immune agonist lipopolysaccharide (LPS). Four inhibitors of mitochondrial respiratory chain Complexes I, III, IV, and V were used (LPS + Mito-Inhibitors) to acutely perturb mitochondrial function, GC sensitivity was quantified using the GC-mimetic dexamethasone (DEX) (LPS + DEX), and the resultant cytokine signatures mapped with a 20-cytokine array. Inhibiting mitochondrial respiration caused large inter-individual differences in LPS-stimulated IL-6 reactivity (Cohen's = 0.72) and TNF-α ( = 1.55) but only minor alteration in EC-based LPS sensitivity ( = 0.21). Specifically, inhibiting mitochondrial Complex IV potentiated LPS-induced IL-6 levels by 13%, but inhibited TNF-α induction by 72%, indicating mitochondrial regulation of the IL-6/TNF-α ratio. As expected, DEX treatment suppressed multiple LPS-induced pro-inflammatory cytokines (IFN-γ, IL-6, IL-8, IL-1β, .TNF-α) by >85% and increased the anti-inflammatory cytokine IL-10 by 80%. Inhibiting Complex I potentiated DEX suppression of IL-6 by a further 12% ( = 0.73), indicating partial mitochondrial modulation of glucocorticoid sensitivity. Finally, to examine if intrinsic mitochondrial respiratory capacity may explain a portion of immune reactivity differences across individuals, we measured biochemical respiratory chain enzyme activities and mitochondrial DNA copy number in isolated peripheral blood mononuclear cells (PBMCs) from a second cohort of 44 healthy individuals in parallel with LPS-stimulated IL-6 and TNF-α response. Respiratory chain .function, particularly Complex IV activity, was positively correlated with LPS-stimulated IL-6 levels (r = 0.45, p = 0.002). Overall, these data provide preliminary evidence that mitochondrial behavior modulates LPS-induced inflammatory cytokine signatures in human blood.
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http://dx.doi.org/10.1016/j.bbih.2020.100080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561023PMC
May 2020

Association of working conditions including digital technology use and systemic inflammation among employees: study protocol for a systematic review.

Syst Rev 2020 09 28;9(1):221. Epub 2020 Sep 28.

Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, Ludwig-Maximilians-University of Munich, Ziemssenstraße 1, 80336, München, Germany.

Background: With the dynamic advancement of digitalization, working environments are changing and risk for employee stress may be increasing. Work stress has been associated with a dysregulation of inflammatory processes as a component of immune function. Systemic low-grade inflammation is discussed as a key player in the relation between stress exposure and chronic illness, such as cardiovascular diseases. The objective of this investigation will be to evaluate the association of working conditions including digital technology use and systemic inflammation among employees.

Methods: We designed and registered a study protocol for a systematic review of randomized controlled trials and prospective non-randomized studies (e.g., cohort, interrupted time series, or before-after studies). We will include studies conducted among adult workers reporting associations of working conditions and inflammatory activity. The outcome will be biomarkers of systemic low-grade inflammation on cell, plasma molecule and intracellular level, such as C-reactive protein, or different types of leukocytes, cytokines, etc. Literature searches will be conducted in several electronic databases (from January 1982 onwards), including PubMed/MEDLINE, Embase, PsycINFO, Web of Science, and CENTRAL. Two reviewers will independently screen all retrieved records, full-text articles, and extract data. The study methodological quality (or bias) will be appraised using appropriate tools. Our results will be described qualitatively. Random effects meta-analysis will be conducted, if feasible and appropriate. Additional analyses will be performed to explore potential sources of heterogeneity.

Discussion: This systematic review and meta-analysis will provide a synthesis of studies evaluating the association of working conditions and systemic inflammation. We anticipate our findings to identify knowledge gaps in the literature that future research should address. Moreover, results of our review may provide implications for corporate and public policy action for employee health promotion and prevention of occupational stress.

Systematic Review Registration: PROSPERO ID: CRD42020166887.
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http://dx.doi.org/10.1186/s13643-020-01463-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523305PMC
September 2020

Associations between Attention and Implicit Associative Learning in Healthy Adults: The Role of Cortisol and Salivary Alpha-Amylase Responses to an Acute Stressor.

Brain Sci 2020 Aug 12;10(8). Epub 2020 Aug 12.

Department of Psychology, Friedrich-Alexander University Erlangen-Nürnberg, 91052 Erlangen, Germany.

In this study, we investigated the associations between implicit associative learning with the cortisol and salivary alpha-amylase (sAA) stress response to an acute stressor as well as their associations with attention. Eighty one healthy adults (25 male) participated and either performed the socially evaluated cold-pressor test (SECPT) or a warm-water control task (WWT). Either prior to or immediately after the SECPT/WWT, participants implicitly learned digit-symbol pairs. A not-previously announced recall test was conducted about 20 min after the SECPT/WWT. Attention was assessed by means of a Stroop task at nine time points over the course of the experiment. Memory recall performance was not significantly associated with the acquisition time point (pre or post stressor) and did not significantly differ between the responder groups (i.e., non-responders, sAA-and-cortisol responders, only sAA responders, and only cortisol responders). Attentional performance increased throughout the experiment (i.e., reaction times in the Stroop task decreased). No differences in the attentional time course were found between the responder groups. However, some associations were found ( < 0.05) that did not pass the multiple comparison adjusted alpha level of α = 0.002, indicating different associations between attention and implicit learning between the responder groups. We conclude that the associations of sAA and cortisol responses with implicit learning are complex and are related to each other. Further studies in which both (sAA and cortisol responses) are selectively (de-) activated are needed. Furthermore, different learning tasks and less-potentially stressful-attentional assessments should be used in future research. Moreover, field studies are needed in which the associations between acute stress and implicit associative learning are investigated in everyday life.
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http://dx.doi.org/10.3390/brainsci10080544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463622PMC
August 2020

Resistance training as an acute stressor in healthy young men: associations with heart rate variability, alpha-amylase, and cortisol levels.

Stress 2021 05 3;24(3):318-330. Epub 2020 Aug 3.

Department of Psychology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.

Regular resistance training has been shown to have many physiological and psychological health benefits. However, the underlying physiological processes are not yet fully understood. One explanation is that resistance training acts like an acute stressor and modulates physiological pathways that are associated with the stress response such as the sympathetic nervous system (SNS), the parasympathetic nervous system (PNS), and the hypothalamic-pituitary-adrenal (HPA) axis. This was systematically investigated in our study. Participants were 45 healthy men who had been doing resistance training regularly for at least nine months. Salivary α-amylase and heart rate that were used as markers for SNS activity increased during the training and decreased afterwards. PNS activity that was assessed by means of heart rate variability parameters decreased during the training and increased after it. Salivary cortisol that was used as marker for HPA axis activity decreased throughout the session. Furthermore, an improvement of positive affect was found after the training. However, additional analyses indicated that the physiological response patterns were found for participants who chose upper-body exercises (in contrast to lower-body exercises) only. Therefore, we were able to show that an upper-body resistance training acts partially like an acute stressor which leads to the typical SNS and PNS - but not HPA axis - stress responses. We conclude that resistance trainings might be an alternative to classical relaxation programs which would have the additional advantage that it is a physical training at the same time. However, more research is needed to develop specific trainings which entirely fulfill this goal.
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http://dx.doi.org/10.1080/10253890.2020.1799193DOI Listing
May 2021

Safety of a Combined WB-EMS and High-Protein Diet Intervention in Sarcopenic Obese Elderly Men.

Clin Interv Aging 2020 24;15:953-967. Epub 2020 Jun 24.

Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nuremberg, Germany.

Purpose: Whole-body electromyostimulation (WB-EMS) especially in combination with a high-protein supplementation has been established as an efficient treatment against sarcopenia. However, there are several case reports of rhabdomyolysis after WB-EMS application. Thus, we asked if this training could potentially lead to deteriorations of the cardiac as well as the renal function.

Materials And Methods: One hundred sarcopenic obese men aged 70 years and older were randomly balanced (1-1-1) and allocated to one of the three study arms. During 16 weeks of intervention, these groups either performed WB-EMS and took a protein supplement (WB-EMS&P), solely received the protein supplement (Protein) or served as control group (CG). WB-EMS consisted of 1.5×20 min (85 Hz, 350 μs, 4 s of strain to 4 s of rest) applied with moderate-to-high intensity while moving. We further generated a daily protein intake of 1.7-1.8 g/kg/body mass per day. At baseline and 8-10 days after completion of the intervention, blood was drawn and biomarkers of muscle, cardiac and renal health were assessed.

Results: Hereby, we found slight but significant elevations of creatine kinase (CK) levels in the WB-EMS group pointing to minor damages of the skeletal muscle (140 U/l [81-210], p < 0.001). This was accompanied by a significant, low-grade increase of creatine kinase-muscle brain (CK-MB, 0.43 ng/mL [-0.29-0.96], p < 0.01) and high-sensitivity troponin T (hsTnT, 0.001 ng/mL. [0.000-0.003], p < 0.001) but without a higher risk of developing heart failure according to N-terminal prohormone of brain natriuretic peptide (NT-proBNP, -5.7 pg/mL [-38.8-24.6], p = 0.17). Estimated glomerular filtration rate (eGFR) was impaired neither by the high-protein supplementation alone nor in combination with WB-EMS (CG 76.0 mL/min/1.73 m [71.9-82.2] vs Protein 73.2 mL/min/1.73 m [63.0-78.9] vs WB-EMS&P 74.6 mL/min/1.73 m [62.8-84.1], p = 0.478).

Conclusion: In conclusion, even in the vulnerable group of sarcopenic obese seniors, the combination of WB-EMS with a high-protein intake revealed no short-term, negative impact on the eGFR, but potential consequences for the cardiovascular system need to be addressed in future studies.
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http://dx.doi.org/10.2147/CIA.S248868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322975PMC
October 2020

Childhood Physical Neglect Is Associated With Exaggerated Systemic and Intracellular Inflammatory Responses to Repeated Psychosocial Stress in Adulthood.

Front Psychiatry 2020 5;11:504. Epub 2020 Jun 5.

Department of Psychology, Brandeis University, Waltham, MA, United States.

Experiences of child maltreatment are associated with a host of adverse mental and physical health outcomes in adulthood. Altered reactivity to psychosocial stress exposure may partially explain known associations between early experiences of maltreatment and later life health. The present study focuses on examining whether experiences of child maltreatment are associated with physiological reactions to initial and repeated psychosocial stress in adulthood. To this end, 44 healthy adults (52% male, aged 18-65) completed the Childhood Trauma Questionnaire to provide information about exposure to child maltreatment and completed the Trier Social Stress Test (TSST) on 2 consecutive days. Peripheral blood was collected prior to as well as 30 and 120 min following the TSST on each day. Plasma Interleukin-6 (IL-6) and gene expression of IL-6, IL-1β, nuclear factor-kB (NF-kB), and inhibitor of kB (IkB) were measured from each blood sample. Total CTQ scores were unrelated to plasma IL-6 and gene expression (s > .10) but a history of childhood physical neglect was associated with increased interleukin-1β (β =.35; =.02; R =.19) and nuclear factor-kB (β =.30; p =.046; R =.13) expression following initial stress. Following repeated exposure to the TSST, childhood physical neglect was associated with increased plasma IL-6 reactivity (β =.34; p =.02; R =.16) and increased expression of nuclear factor-kB (β =.31; p =.04; R =.08). Finally, childhood physical neglect was associated with decreased habituation following repeated exposure to the TSST. Other CTQ subscales were not related to plasma IL-6 and gene expression when considered individually. Results from this study are suggestive of a unique effect of childhood physical neglect on the physiological stress response following initial and repeated exposure to a common psychosocial stressor. This provides important directions for future research because the effect of childhood physical neglect on long-term neglect are not well understood and in need of further investigation.
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http://dx.doi.org/10.3389/fpsyt.2020.00504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290130PMC
June 2020

Association of the Salivary Microbiome With Animal Contact During Early Life and Stress-Induced Immune Activation in Healthy Participants.

Front Psychiatry 2020 7;11:353. Epub 2020 May 7.

Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, University of Ulm, Ulm, Germany.

The prevalence of stress-associated somatic and psychiatric disorders is increased in environments offering a narrow relative to a wide range of microbial exposure. Moreover, different animal and human studies suggest that an overreactive immune system not only accompanies stress-associated disorders, but might even be causally involved in their pathogenesis. In support of this hypothesis, we recently showed that urban upbringing in the absence of daily contact with pets, compared to rural upbringing in the presence of daily contact with farm animals, is associated with a more pronounced immune activation following acute psychosocial stressor exposure induced by the Trier Social Stress Test (TSST). Here we employed 16S rRNA gene sequencing to test whether this difference in TSST-induced immune activation between urban upbringing in the absence of daily contact with pets ( = 20) compared with rural upbringing in the presence of daily contact with farm animals ( = 20) is associated with differences in the composition of the salivary microbiome. Although we did not detect any differences in alpha or beta diversity measures of the salivary microbiome between the two experimental groups, statistical analysis revealed that the salivary microbial beta diversity was significantly higher in participants with absolutely no animal contact ( = 5, urban participants) until the age of 15 compared to all other participants ( = 35) reporting either daily contact with farm animals ( = 20, rural participants) or occasional pet contact ( = 15, urban participants). Interestingly, when comparing these urban participants with absolutely no pet contact to the remaining urban participants with occasional pet contact, the former also displayed a significantly higher immune, but not hypothalamic-pituitary-adrenal (HPA) axis or sympathetic nervous system (SNS) activation, following TSST exposure. In summary, we conclude that only urban upbringing with absolutely no animal contact had long-lasting effects on the composition of the salivary microbiome and potentiates the negative consequences of urban upbringing on stress-induced immune activation.
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http://dx.doi.org/10.3389/fpsyt.2020.00353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223923PMC
May 2020

Neuroendocrine coordination and youth behavior problems: A review of studies assessing sympathetic nervous system and hypothalamic-pituitary adrenal axis activity using salivary alpha amylase and salivary cortisol.

Horm Behav 2020 06 21;122:104750. Epub 2020 Apr 21.

Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, United States.

Externalizing and internalizing behavior problems can have deleterious psychosocial consequences for youth. Both sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis activity and reactivity may contribute to behavior problems but have largely been studied separately, with inconsistent findings. Because the SNS and HPA axis interact to carry out physiological processes (e.g., responding to stressors), considering SNS and HPA axis activity jointly may elucidate disparate findings. This review discusses studies that simultaneously assessed SNS and HPA axis (re)activity and youth behavior problems using measures of salivary alpha amylase (sAA) and salivary cortisol. Multiple patterns of SNS and HPA axis coordination were associated with problem behaviors, especially when considering individual differences and youth's psychosocial context. Importantly, many study findings may be artifacts of widespread methodological differences. The reviewed studies lay the foundation for future research on neuroendocrine coordination as a contributing factor to youth problem behaviors and some recommendations for future research are discussed.
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http://dx.doi.org/10.1016/j.yhbeh.2020.104750DOI Listing
June 2020

Activation of the hypothalamic-pituitary adrenal axis in response to a verbal fluency task and associations with task performance.

PLoS One 2020 16;15(4):e0227721. Epub 2020 Apr 16.

Department of Psychology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.

Speech fluency can be impaired in stressful situations. In this study, it was investigated whether a verbal fluency task by itself, i.e. without the presence of any further stressors, induces responses of the hypothalamic-pituitary adrenal (HPA) axis and of the sympathetic nervous system (SNS). The sample consisted of n = 85 participants (68.2% female; 33.3 ± 15.2 years) who performed two consecutive verbal fluency tasks for two minutes each. The categories were either 'stress' or 'disease' and 'animals' or 'foods' which were presented in a randomized order. Three saliva samples were collected, prior to the task (t0), immediately after (t1), and ten minutes after it (t2). Salivary α-amylase and cortisol were assessed. Furthermore, blood pressure, heart rate, and ratings of actual stress perception, level of effort, and tiredness were measured. The verbal fluency task induced a HPA axis response with a maximum cortisol level at t2 which was independent of task performance. Furthermore, perceived stress and effort, as well as tiredness increased after the task. Moreover, tiredness immediately after the task was negatively correlated with task performance. No α-amylase, blood pressure, or heart rate, and therefore SNS, responses were found. Implications for the integrated specificity model are discussed. We conclude that a verbal fluency task acts like an acute stressor that induces a cortisol and a perceived stress response without the need for further (e.g., social-evaluative) stress components. Therefore, it is a less time-consuming alternative to other stress tasks that can be used in field studies with little effort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227721PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161971PMC
July 2020

Salivary Biomarkers in Psychoneuroimmunology.

Curr Opin Behav Sci 2019 Aug 6;28:58-65. Epub 2019 Mar 6.

Chair of Health Psychology, Institute of Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.

As molecular biology advances, an increasing number of proteins are becoming detectable at very low levels in different biological tissues. In this regard, saliva holds vast promise. Unlike blood, saliva can be sampled 1) non-invasively; 2) across all ages (newborn to elderly); 3) in the field; 4) by study participants; and 5) many times per day. With respect to psychoneuroimmunology (PNI), physiological measures of stress such as cortisol have been well characterized. Alpha amylase provides another physiological index of stress; it is a measure of autonomic nervous system activation and is quantifiable in saliva. Other salivary measures, such as inflammatory biomarkers and immunoglobulin A (IgA), provide valuable information pertaining to the effects of stress on inflammation, mucosal immunity, and oral health. Importantly, due to various methodological issues and a lack of strong correlation between saliva and blood measures, investigators should proceed with caution in drawing conclusions from measures of salivary inflammation that pertain to systemic immunity or generalized health.
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http://dx.doi.org/10.1016/j.cobeha.2019.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094032PMC
August 2019

Evaluation of the socially evaluated cold-pressor group test (SECPT-G) in the general population.

PeerJ 2019 13;7:e7521. Epub 2019 Aug 13.

Institute of Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Background: In stress research, economic instruments for introducing acute stress responses are needed. In this study, we investigated whether the socially evaluated cold-pressor group test (SECPT-G) induces salivary alpha-amylase (sAA) and/or cortisol responses in the general population and whether this is associated with anthropometric, experimental, and lifestyle factors.

Methods: A sample of 91 participants from the general population was recruited. Salivary cortisol and sAA levels were assessed prior to ( ), immediately after ( ), and 10 min after the SECPT-G ( ).

Results: A robust cortisol increase was found immediately after the SECPT-G, which further increased between and . This was independent of most of the control variables. However, men showed a trend toward higher cortisol increases than women ( = 0.005). No sAA responses were found at all. However, sAA levels were dependent on measurement time point with highest levels between 9 pm and 9:30 pm. Participants who immersed their hands into the ice water for the maximally allowed time of 3 min showed higher sAA levels at all time points than participants who removed their hands from the water earlier.

Conclusions: We conclude that the SECPT-G is a good means of an acute stress test when cortisol-but not necessarily sAA-responses are intended.
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http://dx.doi.org/10.7717/peerj.7521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697040PMC
August 2019

Age differences in the relationship between cortisol and emotional memory.

Psychol Aging 2019 Aug 10;34(5):655-664. Epub 2019 Jun 10.

Department of Psychology.

Research has shown that remembering emotional information can occur at the expense of surrounding neutral background information; this emotional memory trade-off occurs similarly in both younger and older adults. We investigated how levels of cortisol, a hormone that acts on the central nervous system, impact emotional memory with age. Younger and older adult participants incidentally encoded emotional (positive, negative, or neutral) items placed on neutral backgrounds and later completed recognition tests for both the items and the backgrounds. Cortisol was measured at multiple time points to assess basal cortisol. Results are reported for prelearning levels, as findings were comparable across time points. Results revealed that higher levels of cortisol predicted a lower memory trade-off effect for older adults compared to younger adults and that this age difference in the role of cortisol tended to be strongest for memory for negative items (rather than for backgrounds or neutral items). No such interaction emerged for the positive trade-off effect. These results suggest that cortisol levels play a different role in supporting emotional memory across the life span, with lower levels of cortisol potentially more adaptive for memory for negative emotional information and higher levels indicating potential impairment with age. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/pag0000367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682424PMC
August 2019

Time course of the physiological stress response to an acute stressor and its associations with the primacy and recency effect of the serial position curve.

PLoS One 2019 17;14(5):e0213883. Epub 2019 May 17.

Department of Psychology, Chair of Health Psychology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

Whether stress affects memory depends on which stress pathway becomes activated and which specific memory system is involved. The activation of the sympathetic nervous system (SNS), leads to a release of catecholamines. The activation of the hypothalamic-pituitary-adrenal (HPA) axis, leads to a release of glucocorticoids. In thus study, it was investigated whether SNS and/or HPA axis activation are associated with long-term memory (LTM) and/or working memory (WM) performance in humans. Thirty-three participants underwent the socially evaluated cold-pressor test. Salivary alpha-amylase (sAA) was used as a marker for the activation of the SNS and cortisol as marker for HPA axis activation. Memory was assessed by means of word lists with 15 words each. The primacy effect (i.e., the correctly recalled words from the beginning of the lists) of the serial position curve was considered as indicator for LTM. The recency effect (i.e., the correctly recalled words from the end of the lists) were used as estimator for WM performance. In sAA responders, the recency effect and, therefore, WM performance increased immediately after the stressor. This was not found in sAA non-responders. In cortisol responders, the primacy effect and, thus, LTM performance decreased 20 minutes after the stressor. No change in LTM performance was found in cortisol non-responders. Our study supports the assumptions that 1) SNS activation is associated with WM processes via stimulation of the prefrontal cortex, and 2) HPA axis activation is associated with LTM processes through interactions with the hippocampus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213883PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524805PMC
January 2020

The Stress and Adversity Inventory for Adults (Adult STRAIN) in German: An overview and initial validation.

PLoS One 2019 9;14(5):e0216419. Epub 2019 May 9.

Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, United States of America.

Life stress is a key determinant of poor mental and physical health, but until recently no instrument existed for efficiently assessing cumulative stress exposure and severity across the entire lifespan. The Stress and Adversity Inventory (STRAIN) is an online, interview-based stress assessment system that was developed to address this need. We examined the concurrent, predictive, and discriminant validity of a German translation of the STRAIN by administering the instrument, along with several other measures of stress and health, to 298 adults (81 men, 217 women, Mage = 30.3 years). The German STRAIN demonstrated excellent concurrent validity, as evidenced by associations with other instruments assessing early adversity (|rs|≥.62, ps≤.001). It also correlated with instruments assessing recent life event exposure in adulthood (|rs|≥.48, ps≤.001), as well as recent perceived stress (|rs|≥ .25, ps≤.001) and recent chronic stress levels (|rs|≥ .19, ps≤.001). Additionally, the German STRAIN showed strong predictive validity in relation to anxiety symptoms (|rs|≥ .22, ps≤.001) and depressive symptoms (|rs|≥ .33, ps≤.001). Finally, the German STRAIN showed good discriminant validity, with lifetime stressor count being unrelated to personality features like neuroticism. These results demonstrate that the German version of the STRAIN is a valid tool for assessing lifetime stress exposure and severity. Additional research is needed to examine how the German STRAIN predicts psychological and biological stress reactivity and physical health outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216419PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508721PMC
January 2020

Health and Disease-Emergent States Resulting From Adaptive Social and Biological Network Interactions.

Front Med (Lausanne) 2019 28;6:59. Epub 2019 Mar 28.

Department Geriatric Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

Health is an adaptive state unique to each person. This subjective state must be distinguished from the objective state of disease. The experience of health and illness (or poor health) can occur both in the absence and presence of objective disease. Given that the subjective experience of health, as well as the finding of objective disease in the community, follow a Pareto distribution, the following questions arise: What are the processes that allow the emergence of four observable states-(1) subjective health in the absence of objective disease, (2) subjective health in the presence of objective disease, (3) illness in the absence of objective disease, and (4) illness in the presence of objective disease? If we consider each individual as a unique biological system, these four health states must emerge from physiological network structures and personal behaviors. The underlying physiological mechanisms primarily arise from the dynamics of external environmental and internal patho/physiological stimuli, which activate regulatory systems including the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Together with other systems, they enable feedback interactions between all of the person's system domains and impact on his system's entropy. These interactions affect individual behaviors, emotional, and cognitive responses, as well as molecular, cellular, and organ system level functions. This paper explores the hypothesis that health is an emergent state that arises from hierarchical network interactions between a person's external environment and internal physiology. As a result, the concept of health synthesizes available qualitative and quantitative evidence of interdependencies and constraints that indicate its top-down and bottom-up causative mechanisms. Thus, to provide effective care, we must use strategies that combine person-centeredness with the scientific approaches that address the molecular network physiology, which together underpin health and disease. Moreover, we propose that good health can also be promoted by strengthening resilience and self-efficacy at the personal and social level, and via cohesion at the population level. Understanding health as a state that is both individualized and that emerges from multi-scale interdependencies between microlevel physiological mechanisms of health and disease and macrolevel societal domains may provide the basis for a new public discourse for health service and health system redesign.
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http://dx.doi.org/10.3389/fmed.2019.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447670PMC
March 2019

The effect of perceived appearance judgements on psychological and biological stress processes across adulthood.

Stress Health 2019 Aug 17;35(3):318-329. Epub 2019 May 17.

Department of Psychology, Brandeis University, Waltham, Massachusetts.

Social self-preservation theory posits that stress is experienced when an aspect of an individual's identity has the potential to be negatively evaluated. Appearance is a central part of identity; however, little research has examined whether perceived appearance judgements are a source of social-evaluative stress. In addition, stress may be an explanatory link in the association between appearance perceptions and depressive symptoms. This study examined whether perceived appearance judgements were associated with increased stress and greater depressive symptoms among adults. Study 1 examined the associations between self-reported appearance judgements and cortisol stress responses in response to a laboratory stressor (Trier Social Stress Test) among 71 individuals aged 18-65. Study 2 assessed self-reported appearance judgements and depressive symptoms among 498 adults ages 18-65 via an online survey data collection. Appearance judgement was associated with a stronger cortisol response, higher self-reported stress, and greater depressive symptoms. Stress mediated all associations between appearance judgements and depressive symptoms and neither age nor gender moderated these associations. The findings suggest that appearance judgements contribute to psychological and biological stress processes and demonstrated that stress mediated the association between appearance judgements and depressive symptoms.
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http://dx.doi.org/10.1002/smi.2863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711807PMC
August 2019

Stress and inflammation - The need to address the gap in the transition between acute and chronic stress effects.

Authors:
Nicolas Rohleder

Psychoneuroendocrinology 2019 07 20;105:164-171. Epub 2019 Feb 20.

Chair of Health Psychology, Institute of Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nägelsbachstr. 49a, 91052, Erlangen, Germany. Electronic address:

Stress responses help us navigate our environment and respond appropriately to threats. Stress systems communicate threats to the entire organism, and as such, also stimulate inflammatory mechanisms. This modulation might serve protective functions in the short term, but sustained low-grade inflammation has severe long-term health consequences. While we have reached a reasonable level of understanding of acute, as well as chronic stress effects on inflammatory mechanisms, there is a significant gap in our understanding of the transitional phase between acute and chronic stress. The purpose of this review is to first summarize current knowledge of our understanding of acute stress effects on inflammation, as well as of chronic stress effects on inflammation, and to then analyze the state of knowledge about the transitional phase between acute and chronic stress. Research discussed here shows that we are beginning to understand the early phase of repeated acute stress, but lack information on longer term exposure to repeated acute stress experiences. More research is needed to bridge this important gap und our conceptualization and understanding of the stress and health relationship.
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http://dx.doi.org/10.1016/j.psyneuen.2019.02.021DOI Listing
July 2019

Associations between symptoms of depression and anxiety and cortisol responses to and recovery from acute stress.

Psychoneuroendocrinology 2019 04 24;102:44-52. Epub 2018 Nov 24.

Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States; Chair of Health Psychology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. Electronic address:

Background: Anxiety disorders and major depressive disorder (MDD) have been associated with increased and blunted HPA axis reactivity to social stress. However, research focusing on associations between HPA axis responses to stress and symptoms of anxiety and depression among individuals without a diagnosis remains an understudied area of research.

Methods: One hundred forty-three adults (52% female) completed the Trier Social Stress Test (TSST). Symptoms of depression and anxiety were assessed prior to the TSST using the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS). HPA axis responses were assessed by measuring salivary cortisol at baseline and following the TSST. Reactivity to and recovery from stress were assessed using multilevel growth modeling controlling for age, BMI, and sex among the full sample and a subset of cortisol responders (n = 72).

Results: Anxiety symptoms were positively associated with flatter recovery slopes among the full sample (t(122.3) = 2.082, p = .039). Among cortisol responders, depression symptoms were associated with steeper reactivity (t(63.32) = 2.53, p = .026) and recovery (t(58.75)=-2.20, p = .03). Anxiety symptoms were associated with marginally flatter reactivity (t(64.00)=-1.97, p = .053) and significantly flatter recovery (t(59.22) = 2.29, p = .025).

Conclusion: Symptoms of anxiety and depression among individuals without a psychiatric diagnosis are associated with blunted and exaggerated cortisol responses to and recovery from stress. Such patterns could indicate increased risk for unhealthy HPA axis dysregulation, allostatic load, and disease.
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http://dx.doi.org/10.1016/j.psyneuen.2018.11.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420396PMC
April 2019

Higher trait reappraisal predicts stronger HPA axis habituation to repeated stress.

Psychoneuroendocrinology 2019 03 23;101:12-18. Epub 2018 Oct 23.

Department of Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany. Electronic address:

Undergoing stress can be advantageous when it leads to adaptation and growth; however, failure of the hypothalamic-pituitary-adrenal (HPA) axis to habituate (i.e., nonhabituation) involves continuing to become highly activated in response to repeated exposure of the same stimulus and is considered maladaptive. Although 50-75% of individuals assessed in a laboratory exhibit adaptive habituation to repeated stress, variability in habituation suggests psychological processes used in response to stress may play a role, such as emotion regulation (ER). Nonetheless, no research to date has investigated whether ER strategies affect HPA axis habituation. We investigated whether tendency to use two ER strategies, reappraisal and suppression, influenced HPA axis habituation among 84 healthy young adults (60.7% female; M = 24.8 years, SD = 6.0) exposed to a standardized experimental stress paradigm on two consecutive days. HPA axis stress responses were assessed using salivary cortisol concentrations. We also examined whether non-manipulated state ER strategies (i.e., those used by the participant during and following the stressor on the first day) modulated HPA axis habituation over and above trait-use in a subsample (N = 60). Trait, but not state, reappraisal was associated with stronger HPA axis habituation. Neither trait nor state suppression were significantly associated with HPA axis habituation. These findings expand our current understanding of how ER can affect stress-related health outcomes and suggest habitual reappraisal plays an important role in adaption of the HPA axis to stress.
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http://dx.doi.org/10.1016/j.psyneuen.2018.10.018DOI Listing
March 2019

Biopsychosocial approach to understanding resilience: Stress habituation and where to intervene.

J Eval Clin Pract 2018 Dec 18;24(6):1339-1346. Epub 2018 Oct 18.

School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia.

Background: Resilience in the face of adversity is a human experience that leads to better health, both mentally and physically. We briefly review its historical origins rooted in ecological biology and its adoption into health care. Resilience is the common response to adversity or potential traumatic events. Individual differences in emotion regulation and coping skills as well as social capital and one's physical environment influence a person's ability to achieve resilience.

Proposed Mechanism: One potential biopsychosocial measure of resilience includes stress habituation to repeated stress as demonstrated in the laboratory, possibly providing a tool to observe mastery of resilience training in the clinic. Evidence-based interventions at the individual and small group level (eg, family, classroom) have successfully shown development of resilient behaviours and improved mental and physical health outcomes. However, the role of social context and public policy clearly influence an individual's ability to be resilient.

Conclusions: Despite the current limited evidence of the effectiveness of resilience building interventions, clinicians, researchers, and other health care professions have an obligation to become advocates for laws and policies that support the most vulnerable, and least resilient, in our society to attain resilience for their health. This salutary effect will enable them to become socially as well as economically productive members of the community at large. It is not possible to remove stress or adversity from life, but we can influence the development of regulatory flexibility and decrease the sociocultural factors linked to the nonresilient experience, thus mitigating adversity's long-term effects on health.
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http://dx.doi.org/10.1111/jep.13052DOI Listing
December 2018

Less immune activation following social stress in rural vs. urban participants raised with regular or no animal contact, respectively.

Proc Natl Acad Sci U S A 2018 05 30;115(20):5259-5264. Epub 2018 Apr 30.

Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and Psychotherapy, Ulm University, 89081 Ulm, Germany;

Urbanization is on the rise, and environments offering a narrow range of microbial exposures are linked to an increased prevalence of both physical and mental disorders. Human and animal studies suggest that an overreactive immune system not only accompanies stress-associated disorders but might even be causally involved in their pathogenesis. Here, we show in young [mean age, years (SD): rural, 25.1 (0.78); urban, 24.5 (0.88)] healthy human volunteers that urban upbringing in the absence of pets ( = 20), relative to rural upbringing in the presence of farm animals ( = 20), was associated with a more pronounced increase in the number of peripheral blood mononuclear cells (PBMCs) and plasma interleukin 6 (IL-6) concentrations following acute psychosocial stress induced by the Trier social stress test (TSST). Moreover, ex vivo-cultured PBMCs from urban participants raised in the absence of animals secreted more IL-6 in response to the T cell-specific mitogen Con A. In turn, antiinflammatory IL-10 secretion was suppressed following TSST in urban participants raised in the absence of animals, suggesting immunoregulatory deficits, relative to rural participants raised in the presence of animals. Questionnaires, plasma cortisol, and salivary α-amylase, however, indicated the experimental protocol was more stressful and anxiogenic for rural participants raised in the presence of animals. Together, our findings support the hypothesis that urban vs. rural upbringing in the absence or presence of animals, respectively, increases vulnerability to stress-associated physical and mental disorders by compromising adequate resolution of systemic immune activation following social stress and, in turn, aggravating stress-associated systemic immune activation.
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http://dx.doi.org/10.1073/pnas.1719866115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960295PMC
May 2018

Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children.

Dev Psychopathol 2019 05 2;31(2):419-431. Epub 2018 Apr 2.

University Hospital Erlangen.

Epigenetic DNA modifications in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine-guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012-.040, ηp2 = 0.03-0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = -0.07, 95% confidence interval [-0.16, -0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.
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http://dx.doi.org/10.1017/S0954579418000056DOI Listing
May 2019
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