Auswirkungen von Belastungen aus Vorgenerationen: Die...

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Auswirkungen von Belastungenaus Vorgenerationen:Die Pforzheim-Studie

Dr. Rupert Linder Dr. Karl Ditzler Tanzi Hoover

Prof. Dr. Gerlinde A.S. Metz

Stress während der Schwangerschaft ist nicht

selten…

Woods et al., AJOG, 2010

Project Ice Storm 1998

Quebec, Kanada

Dr. Suzanne King

World Trade Centre Attack

New York, 2001

Erfahrungen hinterlassen einen biologischen Abdruck

Ein biologischer Abdruck kann an die nächsten Generationen weitergegeben

werden…

Ein biologischer Abdruck kann an die nächsten Generationen weitergegeben

werden…

Ein biologischer Abdruck kann an die nächsten Generationen weitergegeben

werden…

Resiliency

StressStress-

empfindlichkeit

Resilienz

Vorgenerationen bestimmen toxische vs. adaptive

Stressantwort

These: Stress “programmiert” das Krankheitsrisiko der nächsten

Generationen• Psychiatrische • Neurologische • Metabolische • Kardiovaskuläre • Frühgeburten • Andere…

-> Risikobestimmung -> bessere Diagnose -> Therapie

Dr. Tessa Roseboom

Vorgenerationen beeinflussen Krankheitsrisiken:

Dutch Famine Birth CohortAmsterdam, 1944

Bisher keine systematischen Studien über transgenerationales Trauma

Wissenslücken

These: Kriegserfahrungen bestimmen unsere Gesundheit

These: Kriegserfahrungen bestimmen unsere Gesundheit

Es gibt keine “prospektive” Mehrgenerationen-Studie

Pforzheim, 23.Februar 1945

Warum Pforzheim?

Pforzheim 1945: -stärkste Zerstörung -höchster Bevölkerungverlust

Pforzheim heute: -höchster Migrationsanteil -Netzwerk frühe Hilfen

Pforzheim: Idealer Ort für systematische Transgenerationen-Studie

Pforzheim: Idealer Ort für systematische Transgenerationen-Studie

Messungen: •Medizinische Daten •Fragebögen •Biomarker (Epigenetik, Genetik, Metabolik etc.)

Fragebögen: Per Online System

1) Demographics 2) Life Experiences 3) Transgenerational Experiences 4) Adverse Childhood Experiences 5) Current Experiences 6) Rosenberg Scale 7) Substance Exposure Screening 8) Visual Analogue Stress Scale 9) Mental Health Checklist 10) General and Mental Health 11) TSQ and DSM-IV Chart - Screens for PTSD 12) Physical Activity Questionnaire 13) Social Support Questionnaire 14) Partner Relationship 15) Husband/Partner Support Questionnaire 16) Migration: Family History Questionnaire 17) Bicultural Identity Integration 18) Patient Health Questionnaire (PHQ-9)

Fragebögen: Per Online System

Erste Erfolge

Erste Erfolge

Dr. Thomas Bernar, Dr. Rupert Linder, Team Prof. Dr. Thomas Schuster

Erste Erfolge

• Olson DM, Bremeault-Phillips S, King S, Metz GAS, Montesanti S, Olson JK, Hyde A, Pike A, Hoover T, Linder R, Joggerst B, Watts R (submitted) Recent Canadian efforts to develop population-level pregnancy intervention studies to mitigate effects of natural disasters and other tragedies. DOHAD Journal.

• Hoover T, Linder R, Olson DM, Joggerst B, Metz GAS (2018) Study of personal and transgenerational stress on maternal and fetal health in Pforzheim. Canadian National Perinatal Research Meeting, Banff, Canada.

INTRODUCTION

Contemporary epigenetic research shows that stress may alter neurodevelopment and metabolic health due to disruption in an individual’s hypothalamic-pituitary-adrenal (HPA) axis influencing subsequent generations Offspring exposed to ancestral stress may be at risk for anxiety, depression, autism, ADHD, and schizophrenia (Franklin et al., 2012). Previous research is based on cohorts that were subject to starvation/plenty, or on animal models in which stressors were laboratory based. It is presently unknown whether a psychological stress such as war trauma, result in overt physiological stress, still produce transgenerational psychological and physiological disorders. The city of Pforzheim, Germany, is uniquely suited for the study of ancestral stress due to severe destruction in World War II on February 23, 1945.

Theory: Transgenerational epigenetic inheritance. Adverse experience can alter gene expression and under some circumstances have transgenerational influences. Hypothesis: We expect that the bombing of Pforzheim results in recognizable psychological and physiological effects.

PRELIMINARY DATAMETHODS •Pregnant woman will be recruited at their first presentation at a doctor’s office. Maternal health and offspring development will be recorded and linked to ancestral exposure of the Pforzheim bombing (i.e., ancestral F0 generation). •A nested-case control will be use demographic information to separate controls from lineage affected by the bombing. •Questionnaires measuring stress response, ancestral history of adverse experiences, depression, and resilience will be completed at regular intervals. •At birth, cord blood and placenta samples will be collected; saliva, blood, urine, hair will be collected at various time points. Analysis will include inflammatory and endocrine markers, metabolomics, elementomics, DNA methylation, mRNA and miRNA expression (epigenetic/ transcription factor domain, miR-200b, STAT5, ZEB 1,2 in placenta and leukocytes; inflammatory domain, plasma, placenta and leukocyte content/output of IL-1β, IL-6, IL-10 and C-reactive protein; the endocrine domain, plasma concentrations of cortisol, adreno-corticotropic hormone.

Preliminary data shows that Pforzheim has higher rates of low/very low birth weight per 1,000 births, and children obesity rates for ages 4 to 5 are higher than the rest of Germany. Male suicide rates, and school entrance language ability needs are significantly higher than the national average.

ACKNOWLEDGEMENTS Canadian Institutes of Health Research National Sciences and Engineering Research Council of Canada

EXPECTED RESULTSBy combining psychological, physiological, metabolic and epigenetic analysis of personal and ancestral adverse experiences, we anticipate the introduction of physical and psychological abnormalities, changes in DNA methylation, miRNA expression in placenta that are predictive of later offspring health outcomes.

CONCLUSIONS & FUTURE DIRECTIONS

• We anticipate that personal and ancestral adverse experiences introduce biological signatures of chronic stress that significantly determine health outcomes in generations of offspring. This study will suggest tools to increase stress resilience and support maternal and fetal health.

• Explore the effects of introducing a resilience-enhancing strategy; such as, a narrative therapy technique (directive and non-directive reflective writing assignments) to mitigate the effects of stress on mothers and children.

www.onlinemilitaryeducation.org

Transgenerational Stress: Impact of WWII Pforzheim Bombing on Maternal OffspringTanzi Hoover1, Rupert Linder2, Brigitte Joggerst4, David M. Olson3, Thomas Bernar5, Gerlinde A.S. Metz11Department of Neuroscience, University of Lethbridge, 4401 University Drive W, Lethbridge, Alberta, Canada T1K 3M4;2Gynecology, Obstetrics, Psychosomatics and Psychotherapy Goethestrasse 9, 75217, Birkenfeld, Germany;3Department of Obstetrics & Gynecology, Pediatrics and Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2;4Landratsamt Enzkreis, Zähringer Allee 3 75177, Pforzheim, Germany;5Helios Klinikum, Kanzlerstraße 2-675175, Pforzheim, Germany.

Weitere Pläne” Können positive Erfahrungen die negativen Konsequenzen

von Vorgenerationenstress kompensieren?

Dr. Kym Rae

Arts Health Program Newcastle, Australia

Die Gomeroi Gaaynggal Studie

Die Gomeroi Gaaynggal Studie

Alberta Wildfires: Fort McMurray 2016

Können positive Erfahrungen Trauma kompensieren?

Alberta Wildfires:Fort McMurray 2016

Intervention: Pennebaker’s (1986)

Expressives Schreiben

Expressives Schreiben fördert Resilienz der Mütter

(Edinburgh Postnatal Depression Scale)

Folgen von Vorgenerationenstress

?????

Nutzen • Resilienz • Metabolische Anpassung

Risiken • Kardiovaskulär • Metabolisch • Alterungsprozesse

Folgen von Vorgenerationenstress

Nutzen • Resilienz • Metabolische Anpassung

Risiken • Kardiovaskulär • Metabolisch • Alterungsprozesse

Folgen von Vorgenerationenstress

Nutzen • Resilienz • Metabolische Anpassung

Risiken • Kardiovaskulär • Metabolisch • Alterungsprozesse

Paxman, Boora, Montina, Laplante, King et al., submitted

Metabolische Biomarker von Stress in Project Ice Storm

Ambeskovic et al., in preparation

Biomarker von Stress: Queensland Flood 2011

1) Verständnis von Krankheitsmechanismen und Ursachen.

2) Erkenntnisse nutzen & Stressresilienz fördern.

3) Biomarker zur Bestimmung des Krankheitsrisikos und Prävention.

4) Entdeckung neuer therapeutischer Marker.

Das wird die Pforzheim-Studie bewirken können:

… ein gesundes Leben beginnt heute

Danksagungen

Alberta Innovates Health SolutionsAlberta Innovates Health SolutionsAlberta Innovates Health Solutions

Alberta Innovates - Health Solutions