ERSCHÖPFUNG, STRESS, RESILIENZ

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1 C E L E N U S K l i n i k e n Lindauer Psychotherapiewochen 2012 Klinische Vorlesung (2. Woche) ERSCHÖPFUNG, STRESS, RESILIENZ ULRICH T. EGLE DORIS CH. KLINGER

2 ERSCHÖPFUNG, STRESS, RESILIENZ! AGENDA I. Grundlagen der Stressverarbeitung II. Stress und Resilienz: Was hält uns gesund, was macht uns krank? III. Körperliche Erkrankung >> z.b. Typ-2-Diabetes mellitus IV. Chronic Fatigue und Fibromyalgie-Syndrom V. Prävention und Therapie

3 C E L E N U S K l i n i k e n Lindauer Psychotherapiewochen 2012 Klinische Vorlesung (2. Woche) ERSCHÖPFUNG, STRESS, RESILIENZ TEIL I: GRUNDLAGEN DER STRESSVERARBEITUNG ULRICH T. EGLE

4 WOHER KOMMT BURN-OUT? Orden für a.o. Leistungen im globalisierten Kapitalismus? Langzeitfolge einer verwöhnenden Kindheit? B U R N O U T Mobbing?! Folge des gehäu4en Au4retens bestimmter Persönlichkeitsstörungen Folge der gesellscha4 lichen Entwicklung zum feminisierten Mann?

5 SOZIALWISSENSCHAFTLICHE ANSÄTZE FÜR BURNOUT Burnout als Vehikel, die Anpassung zwischen Individuum und Organisationsroutinen auf den Begriff zu bringen >> Reflex vs Intention Der flexible Mensch (Richard Sennett: The Corrosion of Character, 1998) Nach den Losungen der neuen Ordnung ist Abhängigkeit eine Sünde Der flexible Mensch ist entwurzelt (Oskar Negt, 2012) >> Beziehungslosigkeit als Grundprinzip der modernen Gesellscha4 >> mangelnde Unterstützung im privaten Bereich finanzielle und personelle Kürzungen bzw. Rationalisierungsmaßnahmen fortschreitende berufliche Spezialisierung sowie stetig steigende Ansprüche allgemeiner Wertewandel und Wertepluralismus Verlust von Zeitrhythmen ( Blackberry-Syndrom) und Ritualen schlechtes Image bestimmter Berufstätigkeiten in der Öffentlichkeit Die wahrha' selbständige Person erweist sich als keineswegs so unabhängig, wie es kulturelle Stereotypien voraussetzen. Im Erwachsenenleben ist eine im gesunden Sinne selbständige Person in der Lage, sich auf andere zu stützen, wenn die Situation es erfordert (John Bowlby, 1973)

6 ARBEITS- UND ORGANISATIONSBEZOGENE EINFLUSSFAKTOREN FÜR BURNOUT nach Körner 2003 Übermaß an Verantwortlichkeit eingeschränkter Tätigkeits- und Handlungsspielraum Mangel an sozialer Unterstützung Rollenkonflikte und Rollenambiguität unmotivierte, aggressive bzw. problembeladene Klientel Organisationsgröße und Arbeitsstrukturen, z. B. Anonymität und mangelnde Transparenz in großen Institutionen mangelndes Feedback sowohl seitens der Klienten als auch seitens der Organisation Mangel an Einflussmöglichkeiten auf das Arbeitsergebnis psychische Belastung bzw. Überlastung durch Faktoren wie Arbeitszeit, Frustrationen, problematische Interaktionen, sich wiederholende belastende Inhalte der sozialen Arbeit Unterforderung, Eintönigkeit der Arbeit geringe Aufstiegsmöglichkeiten/ Gratifikationsprobleme

7 INDIVIDUELLE BEDINGUNGSFAKTOREN FÜR BURNOUT nach Körner 2003 Berufsbezogene Motivation, Handlungsziele und Einstellungen Perfektionsstreben Überidentifikation mit den Klienten hohe soziale Motivation Idealismus, Enthusiasmus, Engagement hohes Verantwortungsbewusstsein Opferbereitscha4 finale Berufsorientierung, d. h. Berufswahl um des Helfens willen, geringe instrumentelle (pragmatisch-existenzielle) Berufsorientierung

8 INDIVIDUELLE BEDINGUNGSFAKTOREN FÜR BURNOUT nach Körner 2003 Persönlichkeitsmerkmale geringes Selbstbewusstsein Verhaltenstyp: Workaholic ( Aktionismus ) externale Kontrollüberzeugungen (positive oder negative Ereignisse werden nicht als Ergebnis des eigenen Handelns wahrgenommen) passive, indirekte bzw. defensive Bewältigungsstile geringe Empathie-Fähigkeit erhöhtes Angstniveau Aggressivität emotionale Labilität

9 KASUISTIK 43-j. Wirtscha4sprofessor mit Burnout-Symptomatik sowie Panikattacken, Schwankschwindel, nicht einstellbarem Hypertonus und ausgeprägter Schlafstörung (< 4 Std./Nacht) eloquent, Gespräch kontrollierend, konfliktscheu, intellektualisierend Std. Arbeitstag bei 7-Tage Woche: zahlreiche Vorträge, Mitarbeit in verschiedenen Gremien In den letzten 5 Jahren insgesamt 25 Tage Urlaub Beruflicher Werdegang: Ø Abitur mit 1,0 > Studiensti4ung des Deutschen Volkes Ø Promotion in Jura/Internat. Recht mit 25 Jahren Ø Anschließend Stipendium für Masterstudium in Wirtscha4swissenscha4en in Harvard mit anschließender Lehrtätigkeit dort Ø Berufung auf Lehrstuhl einer deutschen Privatuniversität mit 34 Jahren Ø Dekan mit 38 Jahren Ø zusätzlich Lehrau4räge in Paris und Bosten Berater mehrerer DAX-Konzern-Vorstände

10 KASUISTIK cont. Kindheitsentwicklung Ø Einzelkind Ø Vater Physiker in der Forschung, Mutter erfolgreiche Schauspielerin Ø konfliktreiche Ehe der Eltern mit lautstarken Auseinandersetzungen Ø Trennung der Eltern als Pat. 4 J. alt Ø Mutter wechselnde Partnerbeziehungen mit Künstlern Ø Pat. als Kind viel allein zuhause Ø Mutter o4 jähzornig (Alkohol/Drogen) > Misshandlung Ø Mutter hohe Erwartungshaltung an Sohn (Delegation) > verbale Entwertungen häufig Ø kath. Pfarrer als außerfamiliäre Vertrauensperson Ø ab 13. Lj. in kath. Internat > häufiger Misshandlungen Ø als Kind schüchtern, bei Peers respektiert, aber wenig integriert Ø Vater emigrierte in USA > viele Jahre wenig Kontakt Ø erst ab 15. Lj. Jährlich mehrere Wochen bei Vater in USA

11 KASUISTIK cont. Familiäre Situation Ø seit 5 J. verheiratet mit emotional kühler Investmentbankerin ( 6 J.), Wochenendbeziehung (über 400km) Ø Mehrfach kurze Affairen im beruflichen Umfeld Ø Ehe kinderlos ( bisher keine Zeit ) Ø keine Hobbys, wenig gemeinsame Aktivitäten Ø Zusammenhalt v.a. über beruflichen Erfolg > Konkurrenzverhalten Ø keine umschriebenen gemeinsamen Ziele eruierbar Ø kein Verständnis für Burnout seitens Ehefrau ( er braucht halt mal kleine Auszeit, ist ja kein Beinbruch ) Therapieziele Ø Drei Wochen gebe ich mir und Ihnen Zeit, dann habe ich einen wichtigen Vortragstermin in Seattle kriegen Sie das hin?

12 POTENTIELLE AUSWIRKUNGEN VON UNGÜNSTIGEN FRÜHEN UMWELTBEDINGUNGEN AUF DAS WEITERE LEBEN B U R N O U T? ungünstige (frühe) Umweltbedingungen

13

14 E G L E! u. e g l k l i n i k k i n z i g t a l. d e STRESSREGULATION: SYMPATIKUS/PARASYMPATHIKUS

15 STRESSREGULATION: HPA-ACHSE (Sapolsky 1988, McEwen et al 1990) Glukokortikoide (Cortisol) Hypophyse CRH Stress Regulation von Gehirn- und peripheren Funktionen (Stressantwort) Nebennierenrinde Glukokortikoide (Cortisol)

16 STRESS UND ALLOSTASE (Sapolsky 1996; McEwen 2003) Eustress Hypothalamus CRH/AVP LC-NE HPA Cortisol. DHEA Amygdala, Hippocampus, Cortex präfrontalis BD-NF Synaptogenese Adrenalin Noradrenalin adaptives Verhalten Lernen

17 S T R E S S n n Zustand bedrohter biologischer Homöostase (Chrousos & Gold 1992) Stress aktiviert genetisch determinierte neuronale, hormonelle und behaviorale Programme ( Stress-System ) >> Herstellung der biologischen Homöostase/Allostase

18 NORMALE STRESSREAKTION (ALLOSTASE) (McEwen 1998)

19 ALLOSTASE-SYSTEM (McEwen ) HPA-Achse Sympatikus/Parasympathikus Cortisol Dihydroxyepiandrostenol (DHEA) Zytokine Oxytocin Neuropeptid Y Auswirkungen auf Ø Ø Ø Ø ZNS (Kognition, Alterung, Affekt, Diabetes) Stoffwechsel (Diabetes, Fettsucht) kardiovaskuläres System (Arteriosklerose, endotheliale Zellschädigung) Immunsystem (Suppression bzw. verstärkte Reaktion)

20 S T R E S S n n n n n Zustand bedrohter biologischer Homöostase (Chrousos & Gold 1992) Stress aktiviert genetisch determinierte neuronale, hormonelle und behaviorale Programme ( Stress-System ) >> Herstellung der biologischen Homöostase/Allostase Körperliche Schädigungen aktivieren das Stress-System ebenso wie psychosoziale Belastungen Das genetisch determinierte Stress-Verarbeitungssystem rei4 erst in den ersten Lebensjahren aus. Frühe Stresserfahrungen (Bindungsstörung, childhood adversities ) >> eingeschränkte Funktion des Stressverarbeitungssystems >> lebenslang dysfunktionale Stressverarbeitung (Hofer 1996, Meaney et al 1997, 2001, Francis et al 1999)

21 u. e g l k l i n i k k i n z i g t a l. d e u familiäre Gewalt Ø körperliche Ø sexueller u emotionale Misshandlung Missbrauch Vernachlässigung Ø chronisch krankes Elternteil Ø Elternteil psychisch krank/sucht Ø krankes Geschwister Ø Rollenumkehr/Parentifizierung Ø Ein-Eltern-Familie E G L E! u schlechte sozioökonomische Bedingungen

22 STRESS UND ALLOSTASE (Sapolsky 1996; McEwen 2003) Eustress Hypothalamus CRH/AVP LC-NE HPA Cortisol, DHEA Amygdala, Schädigung von Hippocampus Hippocampus, und medialem Cortex präfrontalis Cortex präfrontalis BD-NF Synaptogenese Disstress CRH/AVP Glukocorticoide Adrenalin Noradrenalin adaptives Verhalten Lernen

23 körperlicher Stress psychischer Stress

24 eingeschränkte Stressdämpfung korreliert negativ mit Symptomstärke Ø anhaltende Dendritenzunahme Ø erhöhte Dendritenverästelung Volumenverlust korreliert negativ mit Symptomstärke med. Prä- frontalcortex Hippo- campus Ø reversibler Dendritenabbau Ø reduzierte Dendritenverästelung Dis- stress Ø reduzierte Neurogenese Ø reversibler Dendritenabbau Amygdala verstärkte Stressantwort korreliert positiv mit Symptomstärke

25 DAUERSTRESS IN KINDHEIT/ERWACHSENENALTER AUSWIRKUNGEN AUF GEHIRN, HORMON- UND IMMUNSYSTEM Karatsoreos & McEwen 2011 n bei Kindern u u u u u u Einschränkung von Größe und Funktion des Präfrontalkortex Vergrößerung der Amygdala Verkleinerung (?) des Hippocampus eingeschränkte Aufmerksamkeit, erhöhter Aktivitätslevel, eingeschränkte Affektregulation und Selbstregulation im Verhalten HPA: höhere basale Cortisolspiegel, flacheres Cortisolprofil, bei Stimulation: ACTH-Antwort nicht auslösbar, normale Cortisolreaktion auf CRH-Test (erhöhte ACTH-Antwort bei Depressiven+Misshandelten) Immunsystem: erhöhte Entzün dungsparameter, geringere HSV- Reaktion n bei Erwachsenen u u u u u u Einschränkung der Größe des Präfrontalkortex Verkleinerung der Amygdala Verkleinerung des Hippocampus, Defizite im deklarativen Gedächtnis Depression, Substanzmissbrauch, PTBS HPA: höhere CRH-Spiegel unterdrückte ACTH- und Cortisol- Antwort auf DEX/CRH-Test Immunsystem: erhöhte Entzündungsparameter, erhöhte T- zytotoxische/t-helfer-ratio, stärkere Typ-IV Hypersensitivität

26 STRESS UND ALLOSTASE (Sapolsky 1996; McEwen 2003) Eustress Hypothalamus CRH/AVP LC-NE HPA Glukocorticoide Amygdala, HYPERTROPHIE Hippocampus, Cortex DER präfrontalis AMYGDALA BD-NF Synaptogenese Disstress CRH/AVP Glukocorticoide Adrenalin Noradrenalin adaptives Verhalten Lernen Somatisierung!

27 PATHOLOGISCHE STRESSVERARBEITUNG (McEwen et al 2006) physiol. Antwort physiol. Antwort wechselnde Belastungen gehäu4e normale Stressantwort Zeit verlängerte Stressantwort Somatisierung Depression keine Erholung Allostatische Belastung physiol. Antwort physiol. Antwort fehlende Adaptation normale Adaptation Zeit inadäquate Stressantwort CFS/Burnout FMS Zeit Zeit

28 Does cellular aging relate to patterns of allostasis? An e`xamination of basal and stress reactive HPA axis activity and telomere length "#$%&#'# A. Janet Tomiyama a,b,c,d, Aoife O'Donovan e,f, Jue Lin g, Eli Puterman e, Alanie Lazaro e, Jessica Chan e, Firdaus S. Dhabhar h, Owen Wolkowitz e, Clemens Kirschbaum i, Elizabeth Blackburn g, Elissa Epel e, "#$%&#'# a Department of Psychology, Rutgers University, NJ, United States Physiology b Department of Nutritional & Behavior Sciences, Rutgers 106 University, (2012) NJ, United States c Institute for Health, Health Care Policy and Aging, Rutgers University, NJ, United States d NJ Institute for Food, Nutrition, and Health, Rutgers University, NJ, United States e Department of Psychiatry, University of California, San Francisco, CA, United States f Veteran's Affairs Medical Center, San Francisco, CA, United States g Department of Biochemistry and Biophysics, University of California, San Francisco, CA, United States h Department of Psychiatry & Behavioral Sciences, Institute for Immunity, Transplantation, & Infection, Stanford University, CA, United States Contents lists available at SciVerse ScienceDirect i Department of Psychology, Technical University of Dresden, Germany Physiology & Behavior allostat 44 info abstract ( )*+,-.%/*#'#)/#!""01112 ( Long-term exposure to stress and its physiological mediators, 3#45#)67*#/#',%$5)8#)!9)!/#)! in particular cortisol, may lead to impaired A.J. Tomiyama :,'%&%;%&#)#)/#) 3#45#)67*#/#',%$5)8#)!9 et al. / Physiology & Behavior telomere maintenance. In this study, we examine if greater cortisol responses to an acute stressor and/or dysregulated patterns of daily cortisol secretion are associated with shorter telomere length. Twenty-three postmenopausal women comprising caregivers for dementia partners ( +9<!=><>>>!?@!$9)8! (n=14) :,'%&%;%&#)#)/#) and age- and BMI-matched noncaregivers provided home sampling of cortisol saliva samples waking, 30 min after waking, and bedtime, We also found that and a 12-hour nocturnal overnight urine and collection. diurnal They were also patterning exposed ( -#$%&#'?*)/#)/#!A'%-#*)# to an acute laboratory stressor throughout ( +9<!=><>>>!?@!$9)8! of cortisol was Fina which they provided saliva samples. Peripheral blood mononuclear cells were isolated from a fasting blood related to telomere length, sample and assayed supporting for telomere length. the As hypothesized, idea!!!!!!b!"cd=!5)/!"cdef from greater cortisol theresponses allostatic to the acuteload stressor model. were associated with shorter telomeres, as were higher overnight ( urinary -#$%&#'?*)/#)/#!A'%-#*)# free cortisol levels and flatter daytime cortisol slopes. diurnal While robustrhythms physiological responses ofto acute cortisol stress serve important contribute functions, the long- to cortisol model that dysregulated term consequences of frequent high stress reactivity may include accelerated telomere shortening. poor health, or are at least associated with poor!!!!!!b!"cd=!5)/!"cdef health ElsevierSpecifically, Inc. All rights reserved. studies we found a flatter diurnal cortisol slope and greater overnight output length of cortisol were related to shorter telomere length. Flattened slopes telome have previously been linked to chronic and acute psychological stress ining b [36], cardiovascular disease outcomes [37], mortality from breast cancer our und [38], and both all-cause and cardiovascular mortality [39]. Our study telome suggests that the flattened diurnal cortisol rhythm may also be related In s Urinary cortisol provides an integrated measure of cortisol during ciated w article Article history: Received 19 August 2011 Received in revised form 9 November 2011 Accepted 16 November 2011 journal homepage: Keywords: Cortisol Allostasis Allostatic load Telomere Cellular aging Stress HPA axis relate to patterns of allostasis? basal and stress reactive HPA axis activity and telomere length 1. Introduction also may have common cellular mechanisms. Telomeres may be one of the common cellular mechanisms linking chronic stress to diseases, Aoife O'Donovan e,f How, does Jue psychological Lin g stress, Eli get under Puterman e the skin to cause deleterious health outcomes? McEwen and colleagues! have put forth a helpful somal DNA from damage.! As mitotic cells divide, telomeres get, Alanie of aging. Lazaro e Telomeres are DNA protein, Jessica complexes Chan e that protect, chromo- en Wolkowitz e, model Clemens describing howkirschbaum the wear-and-tear of repeated physiological responses to psychological stress that are part of allostasis, over time, chromosome fusion, less efficient mitosis, and loss of ability for cell re-!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!"#$%&'()*+&,-%**% i, Elizabeth shorter, Blackburn g leaving the cell vulnerable, Elissa to genomic Epel e, instability, end-to-end ersity, NJ, United States lead to allostatic load (damage due to these fluctuations) and eventually plenishment and thus tissue replenishment [6,7]. Even non-mitotic poor health outcomes. Much population and experimental data support cells may develop shortened telomeres when chronically exposed to ers University, NJ, United States this model [1,2], and it is relatively well established that chronic psychological NJ, United stress States is harmful to health. Stress has been linked longitudi- undergo senescence. Telomere shortening, therefore, represents both oxidative stress [8]. When telomeres shorten to a certain point, cells nd Aging, Rutgers University, nally to todisease accelerated states such as metabolic cellular syndrome, aging. lth, Rutgers University, NJ, United States cardiovascular a marker and mechanism of biological aging [9], as the progression toward senescence can be monitored by telomere shortness and telo- disease, diabetes, and other diseases of aging [3 5]. These general and California, San Francisco, CA, pervasive United States effects of stress may be linked to changes proximal to the mere dysfunction activates p53-mediated cellular damage [10].!!

29 nuscript NIH-PA NIH-PA Author Author Manuscript Manuscript NIH-PA NIH-PA Author Au NIH-PA Author Manuscript NIH-PA IH-PA Author Manuscript NIH-PA Author Manuscript NIH-P NIH-PA Author Manuscript NIH-PA Author Manusc u. e g l k l i n i k k i n z i g t a l. d e Departments Psychosom of Med. Psychiatry 2011 January (J.K.K-G,), ;; 73(1): 73(1): Psychology doi: /psy.0b013e b6. (J.K.K-G, J-P. G.), Medicine (W.B.M.), Janice Molecular K. Kiecolt-Glaser, Virology, Immunology, Ph.D., and Jean-Philippe Medical Genetics Gouin, (W.B.M., M.A., Nan-ping R.G.), The Weng, Ohio M.D., State Ph.D., Institute William for Behavioral B. Malarkey, Medicine M.D., Research David (J.K.K-G, Q. Beversdorf, W.B.M., M.D., R.G.), and The Ronald Ohio Glaser, State University, Ph.D. Columbus, Departments NIH Childhood Public Adversity Access Ohio and Laboratory of Psychiatry of Immunology, (J.K.K-G,), Heightens National Psychology the the Institute Impact (J.K.K-G, on Aging, of J-P. of Later-Life G.), NIH, Medicine Baltimore, (W.B.M.), MD (N-P. W.) Molecular Virology, Immunology, and Medical Genetics (W.B.M., R.G.), The Ohio State Institute for Author Behavioral Caregiving Medicine Manuscript Stress Research on on Telomere (J.K.K-G, Length W.B.M., Length R.G.), and and Inflammation The Ohio State University, Columbus, Abstract Ohio and Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, MD (N-P. W.) Psychosom Janice Objective Previous Med. Author K. Kiecolt-Glaser, research manuscript; Ph.D., Jean-Philippe on the physical available Gouin, health M.A., consequences in PMC 2012 Nan-ping Weng, of childhood January M.D., Ph.D., abuse 1. and other Janice K. Kiecolt-Glaser, Ph.D., Jean-Philippe Gouin, M.A., Nan-ping Weng, M.D., Ph.D., Abstract Published William William adversities B. B. in Malarkey, Malarkey, has final been edited M.D., based M.D., form David David on data as: Q. Q. from Beversdorf, Beversdorf, young or M.D., M.D., middle-aged and Ronald and Ronald adults. Glaser, Glaser, This Ph.D. study Ph.D. addressed the Departments of Psychiatry (J.K.K-G,), Psychology (J.K.K-G, J-P. G.), Medicine (W.B.M.), Departments of Psychiatry (J.K.K-G,), Psychology (J.K.K-G, J-P. G.), Medicine (W.B.M.), Molecular Psychosom question of whether Virology, Med. Immunology, 2011 childhood January abuse and ; Medical 73(1): and other Genetics adversities (W.B.M., doi: /psy.0b013e b6. have lasting, detectable consequences Kiecolt-Glaser et al. Page 14 Objective Previous R.G.), The Ohio State Institute Molecular for inflammation Virology, and Immunology, cell research aging on and late the Medical in physical life, and health Genetics whether consequences (W.B.M., the effects R.G.), are of childhood The large Ohio enough abuse State Institute to be and other for for adversities Behavioral Behavioral has Medicine Medicine been based Research Research on data (J.K.K-G, (J.K.K-G, from young W.B.M., W.B.M., or R.G.), middle-aged The Ohio R.G.), The Ohio adults. State State This University, University, study addressed Columbus, Columbus, the Ohio discernible and Laboratory beyond of that Immunology, of a major National chronic Institute stressor, on dementia Aging, NIH, family Baltimore, caregiving. MD (N-P. W.) Ohio question and Laboratory of whether of childhood Immunology, abuse National and other Institute adversities on Aging, have NIH, lasting, Baltimore, detectable MD consequences (N-P. W.) for Method In inflammation this and community cell aging sample late in of life, 132 and healthy whether older the adults effects (mean are large age enough = 69.70, to SD=10.14), be Childhood Abstract Abstract discernible including 58 beyond dementia Adversity that family of a major caregivers chronic Heightens and stressor, 74 noncaregivers, dementia the family Impact blood caregiving. samples of were Later-Life analyzed for interleukin Objective Previous 6 (IL-6), tumor research necrosis on the factor-alpha physical health (TNF-α), consequences and of telomere childhood length, abuse and a measure other of cell Method In adversities Objective Previous has this been community based research on data sample from the physical young of 132 or healthy middle-aged consequences older adults. adults This of (mean childhood study age addressed abuse = 69.70, and the SD=10.14), other Caregiving aging. Depressive symptoms question adversities of has whether been Stress were childhood based on data on assessed abuse from Telomere by the Center and other young adversities or middle-aged Length for Epidemiological have lasting, adults. detectable This study and consequences addressed Inflammation Studies Depression including 58 dementia family caregivers and 74 noncaregivers, blood samples were analyzed the for Scale for question (CES-D). interleukin inflammation of 6 (IL-6), whether and tumor childhood cell aging necrosis abuse late in factor-alpha and life, other and whether adversities (TNF-α), the effects have and lasting, are telomere large detectable enough length, to consequences bea measure of cell aging. Results After discernible for inflammation Depressive beyond controlling symptoms and that cell of a aging major were for late age, chronic assessed in caregiving life, stressor, and by whether dementia status, Center the gender, family effects for Epidemiological caregiving. body large mass enough index, to Studies beexercise, Depression and discernible beyond that of a major chronic stressor, dementia family caregiving. Scale William sleep, Method In (CES-D). the B. presence Malarkey, this community of multiple M.D., sample childhood David of 132 Q. healthy adversities Beversdorf, older was adults related (mean M.D., age to both and = 69.70, heightened Ronald SD=10.14), Glaser, IL-6 (.37 ± Ph.D..03 vs. including Method In.44 ±.0358 log10 dementia this community pg/ml) family and caregivers sample shorter of and 132 telomeres 74 healthy noncaregivers, (6.51 older adults ± blood.17(mean vs. samples 5.87 age ± were = , analyzed Kb), SD=10.14), compared for to the Results After interleukin including 58 6 (IL-6), dementia controlling tumor family for necrosis caregivers age, caregiving factor-alpha and 74 (TNF-α), noncaregivers, status, gender, and telomere blood body length, samples mass a were index, measure analyzed exercise, of cellfor and absence of adversity; the telomere difference could translate into a 7 15 year difference in sleep, aging. interleukin the Depressive presence 6 (IL-6), symptoms of tumor multiple necrosis were childhood assessed factor-alpha by adversities the (TNF-α), Center was for and Epidemiological related telomere to length, both Studies heightened a measure Depression of IL-6 cell(.37 ±.03 lifespan. Abuse was associated with heightened IL-6 and TNF-α levels, and, for TNF-α, this vs. Scale aging..44 ± (CES-D)..03 Depressive log10 pg/ml) symptoms and were shorter assessed telomeres by the Center (6.51 for ±.17 Epidemiological vs ±.20 Studies Kb), Depression compared to the relationship was magnified in caregivers compared to controls. Moreover, abuse and caregiving absence Scale of (CES-D). adversity; the telomere difference could translate into a 7 15 year difference in status Results After were significantly controlling and for independently age, caregiving associated status, gender, with body higher mass index, levels exercise, of depressive and symptoms. lifespan. sleep, Results After Abuse was the presence controlling associated of multiple for with childhood age, caregiving heightened adversities status, IL-6 was gender, and TNF-α related to body both mass levels, heightened index, and, exercise, for TNF-α, IL-6 (.37 ± and this.03 relationship Conclusions Adverse vs. sleep,.44 the ±.03 presence was log10 magnified pg/ml) of multiple and childhood in caregivers shorter childhood telomeres events adversities compared (6.51 related was ± to.17 controls. related vs. to continued 5.87 to ± both Moreover,.20 heightened Kb), vulnerability compared abuse IL-6 and to among (.37 the caregiving ±.03 older Abstract status adults, absence vs..44 were enhancing ± of.03 significantly adversity; log10 the pg/ml) the impact and telomere and independently of shorter chronic difference telomeres stressors. could associated (6.51 translate Childhood ±.17 with into vs. a higher adversities ± year.20 levels difference Kb), cast of compared depressive a in very to long the symptoms. shadow. lifespan. absence of Abuse adversity; was associated the telomere with difference heightened could IL-6 and translate TNF-α into levels, a 7 15 and, year for difference TNF-α, thisin Conclusions Adverse childhood events are related to continued vulnerability among older Keywords relationship lifespan. Abuse Figure was 1. was magnified associated in caregivers with heightened compared IL-6 to controls. and TNF-α Moreover, levels, and, abuse for and TNF-α, caregiving this adults, status relationship enhancing were Mean significantly was (±SEM) the magnified impact telomere and independently of caregivers length chronic as a function compared stressors. associated of childhood to Childhood with controls. higher adversity. Moreover, levels adversities The of three depressive abuse groups cast and a do symptoms. very caregiving not long shadow. psychoneuroimmunology; status were differ significantly in age, with and means IL-6; independently of TNF-α; (0 adversities), depression; associated with cell (1 higher adversity) aging; levels trauma and of depressive (2 or moresymptoms. Conclusions Adverse adversities). childhood events are related to continued vulnerability among older Keywords adults, Conclusions Adverse enhancing the impact childhood of chronic events stressors. are related Childhood to continued adversities vulnerability cast a very long among shadow. older Janice K. Kiecolt-Glaser, Ph.D., Jean-Philippe Gouin, M.A., Nan-ping Weng, M.D., Ph.D Departments of Psychiatry (J.K.K-G,), Psychology (J.K.K-G, J-P. G.), Medicine (W.B.M.), Molecular Virology, Immunology, and Medical Genetics (W.B.M., R.G.), The Ohio State Insti for Behavioral Medicine Research (J.K.K-G, W.B.M., R.G.), The Ohio State University, Colum Ohio and Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, MD (N-P. W Objective Previous research on the physical health consequences of childhood abuse and othe adversities has been based on data from young or middle-aged adults. This study addressed the question of whether childhood abuse and other adversities have lasting, detectable consequences for inflammation and cell aging late in life, and whether the effects are large enough to be