environmental factors, life events, trauma in the course ... · environmental factors, life events,...

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.

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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.