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Environmental factors, life events, trauma in the course of bipolar disorder F Aldinger, TG Schulze Instute for Psychiatric Phenomics and Genomics, Ludwig-Maximilian-University Munich Objective The eology and clinical course of bipolar disorder (BD) is considered to be determined by ge- nec and environmental factors. Although the kindling hypothesis emphasizes the impact of en- vironmental factors on inial onset, their connecon to the outcome and clinical course has been poorly established. Hence there have been numerous research efforts to invesgate the impact of environmental factors on the clinical course of illness. Our aim is to outline recent research on the impact of environmental determinants on the clinical course of BD. Methods Publicaons (between 2000 and January 2016) dealing with the associaon between environmen- tal factors, life events and the clinical course of BD. Publicaons in the reference lists of suitable papers have been taken into consideraon as well. A narrave overview was performed on eligib- le publicaons. Results The different aspects influencing the clinical course of BD can be categorized follo- wing various approaches. The complexity and mutual interference of the different ca- tegories lead to inconsistent categorizaon in the literature. Therefore, we aban- doned the effort to develop a larger classificaon of the different categories. (Graphik) Infections Maternal exposure to influenza is associated with an increased risk of BD and psy- choc features (1,2). The hypothesis that gestaonal viral infecons increase suscepbility to BD couldn’t be supported by Pang et al. and Mortensen et al. (3,4). They all found a higher seropre- valence in BD with an OR between 2.17 and 3 (5–7). Maternal smoking Two studies showed an increased risk for BD due to maternal smoking du- ring pregnancy (8,9). Unl now there have not been any systemac research protocols dealing with the impact of maternal smoking during pregnancy on the clinical course of BD. Birth complications There is one study which suggests an associaon with 2.5-fold higher risk of BD in onset born by planned cesarean secon (10). Born preterm was associated with a higher risk of BD in one study (11)). Climate Overall mania has its peaks in spring and summer and a third peak in mid of winter while depression shows high occurrence in winter and spring (12,13). Childhood trauma The prevalence of posraumac stress disorder (PTSD) in BD ranges from 16 to 39% (14–16). Childhood trauma in the broader sense is considered to be evident in almost 50% of paents with BD (17). The associaon between childhood trauma and BD in onset and its influence on the clinical course are consistent findings (16,18–20). Childhood trauma influen- ces the clinical course by provoking an earlier age of onset, childhood trauma increases the li- kelihood of a rapid cycling course, the occurrence of psychoc features, the number of life me mood episodes and the risk for suicide ideaon and aempts and increases substance misuse. References 1. Canea SE, Bao Y, Co MDT, Ennis FA, Cruz J, Terajima M, et al. Serological Documentaon of Maternal Influenza Exposure and Bipolar Disorder in Adult Offspring. Am J Psychiatry. 2014;171(5):557–63. 2. Parboosing R, Bao Y, Shen L, Schaefer C a, Brown AS. Gestaonal influenza and bipolar disorder in adult offspring. JAMA psychiatry. 2013;70(7):677–85. 3. Pang D, Syed S, Fine P, Jones PB. No associaon between prenatal viral infecon and depression in later life - A long-term cohort study of 6152 subjects. Can J Psychiat- ry. 2009;54(8):565–70. 4. Mortensen PB, Pedersen CB, Mcgrath JJ, Hougaard DM, Norgaard-Petersen B, Mors O, et al. Neonatal anbodies to infecous agents and risk of bipolar disorder: A po- pulaon-based case-control study. Bipolar Disord. 2011;13(7-8):624–9. 5. Hamdani N, Daban-Huard C, Lajnef M, Richard J-R, Delavest M, Godin O, et al. Relaonship between Toxoplasma gondii infecon and bipolar disorder in a French sample. J Affect Disord. 2013;148(2-3):444–8. 6. Tedla Y, Shibre T, Ali O, Tadele G, Woldeamanuel Y, Asrat D, et al. Serum anbodies to Toxoplasma gondii and Herpesvidae family viruses in individuals with schizophrenia and bipolar disorder: a case-control study. Ethiop Med J. 2011;49(3):211–20. 7. Pearce BD, Kruszon-Moran D, Jones JL. The relaonship between Toxoplasma Gondii infecon and mood disorders in the third naonal health and nutrion survey. Biol Psychiatry. Elsevier Inc.; 2012;72(4):290–5. 8. Ekblad M, Gissler M, Lehtonen L, Korkeila J. Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Arch Gen Psychiatry. American Me- dical Associaon; 2010 Aug 1;67(8):841–9. 9. Tala A, Bao Y, Kaufman J, Shen L, Schaefer C a, Brown AS. Maternal smoking during pregnancy and bipolar disorder in offspring. Am J Psychiatry. 2013;170(10):1178–85. 10. Chudal R, Sourander A, Polo-Kantola P, Hinkka-Yli-Salomäki S, Leh V, Sucksdorff D, et al. Perinatal factors and the risk of bipolar disorder in Finland. J Affect Disord. El- sevier; 2014;155:75–80. 11. Nosar C, Reichenberg A, Murray RM, Cnangius S, Lambe MP, Yin L, et al. Preterm birth and psychiatric disorders in young adult life. Arch Gen Psychiatry. 2012 Jun;69(6):E1–8. 12. Geoffroy PA, Bellivier F, Sco J, Etain B. Seasonality and bipolar disorder: A systemac review, from admission rates to seasonality of symptoms. J Affect Disord. Elsevier; 2014;168:210–33. 13. Dominiak M, Swiecicki L, Rybakowski J. Psychiatric hospitalizaons for affecve disorders in Warsaw, Poland: Effect of season and intensity of sunlight. Psychiatry Res. 2015 Sep 30;229(1-2):287–94. 14. Oo MW, Perlman CA, Wernicke R, Reese HE, Bauer MS, Pollack MH. Posraumac stress disorder in paents with bipolar disorder: A review of prevalence, correlates, and treatment strategies. Bipolar Disord. 2004;6(2):470–9. 15. Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RMA, Petukhova M, et al. Lifeme and 12-month prevalence of bipolar spectrum disorder in the Naonal Comorbidity Survey replicaon. Arch Gen Psychiatry. 2007;64(5):543–52. 16. Etain B, Henry C, Bellivier F, Mathieu F, Leboyer M. Beyond genecs: Childhood affecve trauma in bipolar disorder. Bipolar Disorders. 2008. p. 867–76. 17. Garno JL, Goldberg JF, Ramirez PM, Ritzler BA. Impact of childhood abuse on the clinical course of bipolar disorder. Br J Psychiatry. 2005;186:121–5. 18. Daruy-Filho L, Brietzke E, Lafer B, Grassi-Oliveira R. Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatr Scand. 2011;124(6):427–34. 19. Aas M, Henry C, Andreassen OA, Bellivier F, Melle I, Etain B. The role of childhood trauma in bipolar disorders. Int J bipolar Disord. Springer Berlin Heidelberg; 2016;4(1):2. 20. Fisher H, Hosang G. Childhood Maltreatment and Bipolar Disorder : A Crical Review of the Evidence. Mind Brain. 2010;000(000):1–11. 21. Malkoff-Schwartz S, Frank E, Anderson B, Sherrill JT, Siegel L, Paerson D, et al. Stressful life events and social rhythm disrupon in the onset of manic and depressive bipolar episodes: a preliminary invesgaon. Arch Gen Psychiatry. 1998;55(8):702–7. 22. Hosang GM, Korszun a, Jones L, Jones I, Gray JM, Gunasinghe CM, et al. Adverse life event reporng and worst illness episodes in unipolar and bipolar affecve disorders: measuring environmental risk for genec research. Psychol Med. 2010;40(11):1829–37. 23. Johnson SL. Life events in bipolar disorder: Towards more specific models. Clin Psychol Rev. 2005;25(8):1008–27. 24. Kessing LV, Andersen PK. Predicve effects of previous episodes on the risk of recurrence in depressive and bipolar disorders. Curr Psychiatry Rep. 2005;7(6):413–20. 25. Alloy LB, Abramson LY, Urosevic S, Walshaw PD, Nusslock R, Neeren AM. The psychosocial context of bipolar disorder: Environmental, cognive, and developmental risk factors. Clin Psychol Rev. 2005;25(8):1043–75. 26. Bender RE, Alloy LB. Life stress and kindling in bipolar disorder: Review of the evidence and integraon with emerging biopsychosocial theories. Clin Psychol Rev. Elsevier Ltd; 2011;31(3):383–98. 27. Ellico A, Hammen C, Gitlin M, Brown G, Jamison K. Life events and the course of bipolar disorder. Am J Psychiatry. 1990;147(9):1194–8. 28. Hillegers MHJ, Burger H, Wals M, Reichart CG, Verhulst FC, Nolen W a., et al. Impact of stressful life events, familial loading and their interacon on the onset of mood disorders: Study in a high-risk cohort of adolescent offspring of parents with bipolar disorder. Br J Psychiatry. 2004;185(AUG.):97–101. 29. Hlastala S a, Frank E, Kowalski J, Sherrill JT, Tu XM, Anderson B, et al. Stressful life events, bipolar disorder, and the “kindling model”. J Abnorm Psychol. 2000;109(4):777– 86. 30. Paykel ES. Life events and affecve disorders. Acta Psychiatr Scand. 2003;108(6):61–6. 31. Johnson SL, Cuellar AK, Ruggero C, Wine-Perlman C, Goodnick P, White R, et al. Life events as predictors of mania and depression in bipolar I disorder. J Abnorm Psychol. 2008;117(2):268–77. 32. Koenders MA, Giltay EJ, Spijker AT, Hoencamp E, Spinhoven P, Elzinga BM. Stressful life events in bipolar I and II disorder: Cause or consequence of mood symptoms? J Affect Disord. Elsevier; 2014;161:55–64. 33. Christensen EM, Gjerris A, Larsen JK, Bendtsen BB, Larsen BH, Rolff H, et al. Life events and onset of a new phase in bipolar affecve disorder. Bipolar Disord. 2003;5(5):356– 61. 34. Kim EY, Miklowitz DJ, Biuckians A, Mullen K. Life stress and the course of early-onset bipolar disorder. J Affect Disord. 2007;99(1–3):37–44. 35. Cohen AN, Hammen C, Henry RM, Daley SE. Effects of stress and social support on recurrence in bipolar disorder. J Affect Disord. 2004;82:143–7. 36. Kemner SM, van Haren N, Bootsman F, Eijkemans M, Vonk R, van der Schot AC, et al. The influence of life events on first and recurrent admissions in bipolar disorder. Int J Bipolar Disord. 2015;3(1):6. 37. Greenberg S, Rosenblum KL, McInnis MG, Muzik M. The role of social relaonships in bipolar disorder: A review. Psychiatry Res. Elsevier; 2014;219(2):248–54. 38. Johnson L, Lundström O, Aberg-Wistedt A, Mathé AA. Social support in bipolar disorder: its relevance to remission and relapse. Bipolar Disord. 2003;5(2):129–37. 39. Johnson SL, Wine C a, Meyer B, Greenhouse WJ, Miller I. Social support and the course of bipolar disorder. J Abnorm Psychol. 1999;108(4):558–66. 40. Johnson SL, Meyer B, Wine C, Small J. Social support and self-esteem predict changes in bipolar depression but not mania. J Affect Disord. 2000;58(1):79–86. Acknowledgements This work was supported by Deutsche Forschungsgemeinschaſt (grant no. SCHU 1603/5-1 and SCHU 1603/7-1). Genec associaons between bipolar disorder and childhood trauma Life events Numerous researchers have shown that certain life events influence the age of onset and the clinical course of BD (21–30). The type of stressful life events differs in triggering mania or depression. The literature emphasizes that posive life events and goal aainment are more likely to be followed by mania (23,25,31,32). Others support the point of view that ne- gave as well as posive life events are able to trigger both depression and mania (31,33–35). An increased life event load stands for a higher risk for the first episode as well as subsequent episodes (24,26,36). Life events prior to subsequent episodes were discussed to be caused by the illness itself (24,26,32). Post’s kindling theory emphasizes that external triggers such as life events have a greater impact on the first episode than on subsequent episodes. Social Support The rate of relapse is higher in paents with low social support (37–40). Furthermore the results show that having a partner at onset of illness has a posive effect on the course of illness especially on the remission between episodes (38). Candidate genes Age of onset Suicidality BDNF val66met 5-HTTLPR SLC6A4 TLR2 SNPs near genes coding for calcium channel related proteins CLOCK Conclusion The findings suggest an associaon between environmental factors and the clinical course of BD. Due to various methodological limitaons the results should be considered cauously. Syste- mac longitudinal long term follow-up trials are needed to produce robust results. In the future new therapeuc concepts could be derived from the findings.

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Page 1: Environmental factors, life events, trauma in the course ... · Environmental factors, life events, trauma in the course of bipolar disorder F Aldinger, TG Schulze Institute for Psychiatric

Environmental factors, life events, trauma in the course of bipolar disorder

F Aldinger, TG Schulze InstituteforPsychiatricPhenomicsandGenomics,Ludwig-Maximilian-UniversityMunich

ObjectiveTheetiologyandclinicalcourseofbipolardisorder(BD) isconsideredtobedeterminedbyge-neticandenvironmentalfactors.Althoughthekindlinghypothesisemphasizestheimpactofen-vironmentalfactorsoninitialonset,theirconnectiontotheoutcomeandclinicalcoursehasbeenpoorlyestablished.Hencetherehavebeennumerousresearcheffortstoinvestigatetheimpactofenvironmentalfactorsontheclinicalcourseofillness.OuraimistooutlinerecentresearchontheimpactofenvironmentaldeterminantsontheclinicalcourseofBD.

MethodsPublications(between2000andJanuary2016)dealingwiththeassociationbetweenenvironmen-talfactors,lifeeventsandtheclinicalcourseofBD.Publicationsinthereferencelistsofsuitablepapershavebeentakenintoconsiderationaswell.Anarrativeoverviewwasperformedoneligib-lepublications.

ResultsThe different aspects influencing the clinical course of BD can be categorized follo-wing various approaches. The complexity and mutual interference of the different ca-tegories lead to inconsistent categorization in the literature. Therefore, we aban-doned the effort to develop a larger classification of the different categories. (Graphik)

InfectionsMaternalexposuretoinfluenzaisassociatedwithanincreasedriskofBDandpsy-choticfeatures(1,2).ThehypothesisthatgestationalviralinfectionsincreasesusceptibilitytoBDcouldn’tbesupportedbyPangetal.andMortensenetal.(3,4).Theyallfoundahigherseropre-valenceinBDwithanORbetween2.17and3(5–7).

Maternal smokingTwostudiesshowedanincreasedriskforBDduetomaternalsmokingdu-ringpregnancy(8,9).UntilnowtherehavenotbeenanysystematicresearchprotocolsdealingwiththeimpactofmaternalsmokingduringpregnancyontheclinicalcourseofBD.

Birth complicationsThereisonestudywhichsuggestsanassociationwith2.5-foldhigherriskofBDinonsetbornbyplannedcesareansection(10).BornpretermwasassociatedwithahigherriskofBDinonestudy(11)).

ClimateOverallmaniahasitspeaksinspringandsummerandathirdpeakinmidofwinterwhiledepressionshowshighoccurrenceinwinterandspring(12,13).

Childhood traumaTheprevalenceofposttraumaticstressdisorder(PTSD)inBDrangesfrom16to39%(14–16).Childhoodtraumainthebroadersenseisconsideredtobeevidentinalmost50%ofpatientswithBD(17).TheassociationbetweenchildhoodtraumaandBDinonsetanditsinfluenceontheclinicalcourseareconsistentfindings(16,18–20).Childhoodtraumainfluen-cestheclinicalcoursebyprovokinganearlierageofonset,childhoodtraumaincreasestheli-kelihoodofarapidcyclingcourse,theoccurrenceofpsychoticfeatures,thenumberoflifetimemoodepisodesandtheriskforsuicideideationandattemptsandincreasessubstancemisuse.

References1. CanettaSE,BaoY,CoMDT,EnnisFA,CruzJ,TerajimaM,etal.SerologicalDocumentationofMaternalInfluenzaExposureandBipolarDisorderinAdultOffspring.AmJ

Psychiatry.2014;171(5):557–63.2. ParboosingR,BaoY,ShenL,SchaeferCa,BrownAS.Gestationalinfluenzaandbipolardisorderinadultoffspring.JAMApsychiatry.2013;70(7):677–85.3. PangD,SyedS,FineP,JonesPB.Noassociationbetweenprenatalviralinfectionanddepressioninlaterlife-Along-termcohortstudyof6152subjects.CanJPsychiat-

ry.2009;54(8):565–70.4. MortensenPB,PedersenCB,McgrathJJ,HougaardDM,Norgaard-PetersenB,MorsO,etal.Neonatalantibodiestoinfectiousagentsandriskofbipolardisorder:Apo-

pulation-basedcase-controlstudy.BipolarDisord.2011;13(7-8):624–9.5. HamdaniN,Daban-HuardC,LajnefM,RichardJ-R,DelavestM,GodinO,etal.RelationshipbetweenToxoplasmagondiiinfectionandbipolardisorderinaFrenchsample.

JAffectDisord.2013;148(2-3):444–8.6. TedlaY,ShibreT,AliO,TadeleG,WoldeamanuelY,AsratD,etal.SerumantibodiestoToxoplasmagondiiandHerpesvidaefamilyvirusesinindividualswithschizophrenia

andbipolardisorder:acase-controlstudy.EthiopMedJ.2011;49(3):211–20.7. PearceBD,Kruszon-MoranD,JonesJL.TherelationshipbetweenToxoplasmaGondiiinfectionandmooddisordersinthethirdnationalhealthandnutritionsurvey.Biol

Psychiatry.ElsevierInc.;2012;72(4):290–5.8. EkbladM,GisslerM,LehtonenL,KorkeilaJ.Prenatalsmokingexposureandtheriskofpsychiatricmorbidityintoyoungadulthood.ArchGenPsychiatry.AmericanMe-

dicalAssociation;2010Aug1;67(8):841–9.9. TalatiA,BaoY,KaufmanJ,ShenL,SchaeferCa,BrownAS.Maternalsmokingduringpregnancyandbipolardisorderinoffspring.AmJPsychiatry.2013;170(10):1178–85.10. ChudalR,SouranderA,Polo-KantolaP,Hinkka-Yli-SalomäkiS,LehtiV,SucksdorffD,etal.PerinatalfactorsandtheriskofbipolardisorderinFinland.JAffectDisord.El-

sevier;2014;155:75–80.11. NosartiC,ReichenbergA,MurrayRM,CnattingiusS,LambeMP,YinL,etal.Pretermbirthandpsychiatricdisorders inyoungadult life.ArchGenPsychiatry.2012

Jun;69(6):E1–8.12. GeoffroyPA,BellivierF,ScottJ,EtainB.Seasonalityandbipolardisorder:Asystematicreview,fromadmissionratestoseasonalityofsymptoms.JAffectDisord.Elsevier;

2014;168:210–33.13. DominiakM,SwiecickiL,RybakowskiJ.PsychiatrichospitalizationsforaffectivedisordersinWarsaw,Poland:Effectofseasonandintensityofsunlight.PsychiatryRes.

2015Sep30;229(1-2):287–94.14. OttoMW,PerlmanCA,WernickeR,ReeseHE,BauerMS,PollackMH.Posttraumaticstressdisorderinpatientswithbipolardisorder:Areviewofprevalence,correlates,

andtreatmentstrategies.BipolarDisord.2004;6(2):470–9.15. MerikangasKR,AkiskalHS,AngstJ,GreenbergPE,HirschfeldRMA,PetukhovaM,etal.Lifetimeand12-monthprevalenceofbipolarspectrumdisorderintheNational

ComorbiditySurveyreplication.ArchGenPsychiatry.2007;64(5):543–52.16. EtainB,HenryC,BellivierF,MathieuF,LeboyerM.Beyondgenetics:Childhoodaffectivetraumainbipolardisorder.BipolarDisorders.2008.p.867–76.17. GarnoJL,GoldbergJF,RamirezPM,RitzlerBA.Impactofchildhoodabuseontheclinicalcourseofbipolardisorder.BrJPsychiatry.2005;186:121–5.18. Daruy-FilhoL,BrietzkeE,LaferB,Grassi-OliveiraR.Childhoodmaltreatmentandclinicaloutcomesofbipolardisorder.ActaPsychiatrScand.2011;124(6):427–34.19. AasM,HenryC,AndreassenOA,BellivierF,MelleI,EtainB.Theroleofchildhoodtraumainbipolardisorders.IntJbipolarDisord.SpringerBerlinHeidelberg;2016;4(1):2.20. FisherH,HosangG.ChildhoodMaltreatmentandBipolarDisorder :ACriticalReviewoftheEvidence.MindBrain.2010;000(000):1–11.21. Malkoff-SchwartzS,FrankE,AndersonB,SherrillJT,SiegelL,PattersonD,etal.Stressfullifeeventsandsocialrhythmdisruptionintheonsetofmanicanddepressive

bipolarepisodes:apreliminaryinvestigation.ArchGenPsychiatry.1998;55(8):702–7.22. HosangGM,Korszuna,JonesL,JonesI,GrayJM,GunasingheCM,etal.Adverselifeeventreportingandworstillnessepisodesinunipolarandbipolaraffectivedisorders:

measuringenvironmentalriskforgeneticresearch.PsycholMed.2010;40(11):1829–37.23. JohnsonSL.Lifeeventsinbipolardisorder:Towardsmorespecificmodels.ClinPsycholRev.2005;25(8):1008–27.24. KessingLV,AndersenPK.Predictiveeffectsofpreviousepisodesontheriskofrecurrenceindepressiveandbipolardisorders.CurrPsychiatryRep.2005;7(6):413–20.25. AlloyLB,AbramsonLY,UrosevicS,WalshawPD,NusslockR,NeerenAM.Thepsychosocialcontextofbipolardisorder:Environmental,cognitive,anddevelopmentalrisk

factors.ClinPsycholRev.2005;25(8):1043–75.26. BenderRE,AlloyLB.Lifestressandkindlinginbipolardisorder:Reviewoftheevidenceandintegrationwithemergingbiopsychosocialtheories.ClinPsycholRev.Elsevier

Ltd;2011;31(3):383–98.27. EllicottA,HammenC,GitlinM,BrownG,JamisonK.Lifeeventsandthecourseofbipolardisorder.AmJPsychiatry.1990;147(9):1194–8.28. HillegersMHJ,BurgerH,WalsM,ReichartCG,VerhulstFC,NolenWa.,etal.Impactofstressfullifeevents,familialloadingandtheirinteractionontheonsetofmood

disorders:Studyinahigh-riskcohortofadolescentoffspringofparentswithbipolardisorder.BrJPsychiatry.2004;185(AUG.):97–101.29. HlastalaSa,FrankE,KowalskiJ,SherrillJT,TuXM,AndersonB,etal.Stressfullifeevents,bipolardisorder,andthe“kindlingmodel”.JAbnormPsychol.2000;109(4):777–

86.30. PaykelES.Lifeeventsandaffectivedisorders.ActaPsychiatrScand.2003;108(6):61–6.31. JohnsonSL,CuellarAK,RuggeroC,Winett-PerlmanC,GoodnickP,WhiteR,etal.LifeeventsaspredictorsofmaniaanddepressioninbipolarIdisorder.JAbnormPsychol.

2008;117(2):268–77.32. KoendersMA,GiltayEJ,SpijkerAT,HoencampE,SpinhovenP,ElzingaBM.StressfullifeeventsinbipolarIandIIdisorder:Causeorconsequenceofmoodsymptoms?J

AffectDisord.Elsevier;2014;161:55–64.33. ChristensenEM,GjerrisA,LarsenJK,BendtsenBB,LarsenBH,RolffH,etal.Lifeeventsandonsetofanewphaseinbipolaraffectivedisorder.BipolarDisord.2003;5(5):356–

61.34. KimEY,MiklowitzDJ,BiuckiansA,MullenK.Lifestressandthecourseofearly-onsetbipolardisorder.JAffectDisord.2007;99(1–3):37–44.35. CohenAN,HammenC,HenryRM,DaleySE.Effectsofstressandsocialsupportonrecurrenceinbipolardisorder.JAffectDisord.2004;82:143–7.36. KemnerSM,vanHarenN,BootsmanF,EijkemansM,VonkR,vanderSchotAC,etal.Theinfluenceoflifeeventsonfirstandrecurrentadmissionsinbipolardisorder.Int

JBipolarDisord.2015;3(1):6.37. GreenbergS,RosenblumKL,McInnisMG,MuzikM.Theroleofsocialrelationshipsinbipolardisorder:Areview.PsychiatryRes.Elsevier;2014;219(2):248–54.38. JohnsonL,LundströmO,Aberg-WistedtA,MathéAA.Socialsupportinbipolardisorder:itsrelevancetoremissionandrelapse.BipolarDisord.2003;5(2):129–37.39. JohnsonSL,WinettCa,MeyerB,GreenhouseWJ,MillerI.Socialsupportandthecourseofbipolardisorder.JAbnormPsychol.1999;108(4):558–66.40. JohnsonSL,MeyerB,WinettC,SmallJ.Socialsupportandself-esteempredictchangesinbipolardepressionbutnotmania.JAffectDisord.2000;58(1):79–86.

AcknowledgementsThisworkwassupportedbyDeutscheForschungsgemeinschaft(grantno.SCHU1603/5-1andSCHU1603/7-1).

Genetic associations between bipolar disorder and childhood trauma

Life eventsNumerousresearchershaveshownthatcertainlifeeventsinfluencetheageofonsetandtheclinicalcourseofBD(21–30).Thetypeofstressfullifeeventsdiffersintriggeringmaniaordepression.Theliteratureemphasizesthatpositivelifeeventsandgoalattainmentaremorelikelytobefollowedbymania(23,25,31,32).Otherssupportthepointofviewthatne-gativeaswellaspositivelifeeventsareabletotriggerbothdepressionandmania(31,33–35).Anincreasedlifeeventloadstandsforahigherriskforthefirstepisodeaswellassubsequentepisodes(24,26,36).Lifeeventspriortosubsequentepisodeswerediscussedtobecausedbytheillnessitself(24,26,32).Post’skindlingtheoryemphasizesthatexternaltriggerssuchaslifeeventshaveagreaterimpactonthefirstepisodethanonsubsequentepisodes.

Social Support Therateofrelapseishigherinpatientswithlowsocialsupport(37–40).Furthermoretheresultsshowthathavingapartneratonsetofillnesshasapositiveeffectonthecourseofillnessespeciallyontheremissionbetweenepisodes(38).

Candidate genes Age of onset Suicidality

BDNF val66met

5-HTTLPR SLC6A4

TLR2

SNPs near genes coding for calcium channel related proteins

CLOCK

ConclusionThefindingssuggestanassociationbetweenenvironmentalfactorsandtheclinicalcourseofBD.Duetovariousmethodologicallimitationstheresultsshouldbeconsideredcautiously.Syste-maticlongitudinallongtermfollow-uptrialsareneededtoproducerobustresults.Inthefuturenewtherapeuticconceptscouldbederivedfromthefindings.

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Counseling to Protect · The development process is complicated, not always linear, and may be influenced by other factors: • Experiences of trauma: Trauma can delay a child’s

Further modelling of some major factors influencing road trauma

Factors Affecting Mortality in Older Trauma Patients - A ...eprints.whiterose.ac.uk/96827/3/SammyI Meta-analysis 16Mar16.pdf · This is an author produced version of Factors Affecting

Various factors can impact brain development: 1.Direct CNS injury or insult (e.g., stroke, tumor, trauma) 2.Environmental factors (e.g., malnutrition,

Anesthesia for Orthopedic Trauma - IntechOpen · Anesthesia for Orthopedic Trauma 189 2.1.5 Liver disease The liver is responsible for protein synthesis (albumin, coagulation factors,

Trauma-Informed Approach to Prevention - KPFPSocio-economic factors refer to income, education, and occupation. Socio-economic factors are important data points because they have a

Aldinger v. Howard, 427 U.S. 1 (1976)

Factors affecting mortality in patients with thorax trauma

Die Autoren dieses Buches - Springer978-3-322-90812-4/1.pdf · Die Autoren dieses Buches Kai Aldinger Dipl-Informatiker Kai Aldinger hat an der Universität Stutt gart Informatik

Using Trauma and Culture Lens with the Protective Factors Framework

How to create a trauma responsive environment: Covid-19 … · 2020. 7. 7. · How to Create a Trauma Responsive Environment: Covid-19 Protective Factors and Responses Welcome! •

Original Article - SciELO · trauma, hospital admission and the ICU stay, several factors remain associated with the death of the most severe cases. Early identification of factors

Supporting Students Affected by Trauma...trauma terminology, risk and protective factors, resiliency, evidence-based strategies, and diversity considerations. The brief also provides

Trauma Related Infections Research Area annual report_2017_IDCRP website.pdf · factors associated with infections. Describe the infectious disease epidemiology of trauma-related

Trauma in Young Permanent Teeth: Factors Associated with

Trauma and Brain Development: A Protective Factors Approach

Aldinger, Maggie_ Google Maps.docx · Web viewLets Take a Walk By: Maggie Aldinger Assessment Criteria Criterion A: Knowing & understanding Maximum: 8 Students should be able to:

Vom Geheimnis traditioneller Hausformen Rathaus Esslingen am Neckar Betrachtungen von Karl Aldinger November 2010

Screening for Acute Factors That Predict Pain Post Trauma: A Pilot Study