University of Groningen Adverse life events and overweight in childhood, adolescence and young adulthood Elsenburg, Leonie Koosje

Adverse life events and overweight in childhood, adolescence and young adulthood Elsenburg, Leonie Koosje

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Elsenburg, L. K. (2018). Adverse life events and overweight in childhood, adolescence and young adulthood. Rijksuniversiteit Groningen.

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Chapter(7(

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General(discussion(

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Against!the!background!of!a!dramatic!rise!in!overweight!and!obesity!prevalence!at!the!end! of!the!20th!_{century,!the!American!Academy!of!Pediatrics!(AAP)!recommended!pediatricians!}

in!2003!to!routinely!assess!and!guide!children!in!their!diet!and!physical!activity!practices![1].! Diet!and!physical!activity!are!considered!the!main!drivers!of!the!obesity!epidemic.!Since!the! beginning! of! this! century,! the! effect! of! sedentary! behavior! (i.e.! any! waking! behavior! characterized! by! a! very! low! energy! expenditure! while! sitting,! reclining! or! lying)! has! increasingly!been!evaluated!and!targeted!by!overweight!and!obesity!prevention!programs!in! children! [2].! However,! effects! of! programs! tackling! these! behaviors! on! overweight! and! obesity!prevention!and!reduction!are!only!modest,!encouraging!researchers!to!think!beyond! these! classic! determinants! of! overweight! and! obesity! [3].! An! increasing! body! of! research! now! examines! the! role! of! psychosocial! stressors! in! the! development! of! overweight! and! obesity![3,4].!An!important!psychosocial!stressor!in!this!context!is!the!experience!of!adverse! life! events.! Adverse! life! events! are! events! such! as! childhood! abuse,! illness! or! death! of! a! family! member! or! friend! and! parental! divorce.! The! focus! of! this! dissertation! was! on! the! relation!between!adverse!life!events!and!body!mass!index!(BMI)!in!children,!adolescents!and! young!adults.!!

In!this!chapter,!I!will!provide!a!summary!of!the!main!findings!of!this!dissertation!and! discuss!their!implications.!I!will!provide!explanations!for!why!certain!associations!between! accumulation!of!adverse!life!events!and!BMI!and!between!childhood!abuse!and!BMI!were! identified,! while! others! were! not.! Firstly,! I! will! focus! on! factors! that! could! influence! the! relationship!between!adverse!events!and!BMI.!Secondly,!the!existence!of!a!time!lag!between! exposure! and! outcome! will! be! considered.! Thirdly,! gender! differences! in! the! associations! between!adverse!life!events!and!BMI!will!be!discussed.!Suggestions!for!obesity!prevention! and! intervention! programs! and! areas! for! future! research! will! be! given.! This! chapter! will! conclude!with!methodological!considerations!in!accumulation!of!adverse!events!research.! (

MAIN(FINDINGS(

The! first! research! question! of! this! dissertation! was! whether! there! was! an! association! between! accumulation! of! adverse! life! events! and! measures! of! overweight! in! childhood,! adolescence!and!young!adulthood.!The!results!of!the!systematic!review!and!metaSanalysis! indicated! a! small! positive! association! between! accumulation! of! adverse! life! events! and! measures! of! overweight! (i.e.! overweight,! obesity! and! BMI)! in! childhood! and! adolescence! (chapter(2).!However,!the!number!of!included!studies!was!small!and!heterogeneity!between! studies! with! regard! to! measurement! of! adverse! life! events! and! construction! of! an! accumulated!adverse!life!events!measure!was!large.!In!addition,!longitudinal!cohort!studies! investigating! the! association! between! accumulation! of! adverse! life! events! and! overweight! measures! in! adolescence! were! scarce.! In! a! longitudinal! investigation! using! TRAILS! data,! a!

Dutch!cohort!study!following!adolescents!into!young!adulthood,!no!associations!were!found! between!accumulation!of!adverse!life!events!and!BMI!in!children!and!adolescents!(chapter( 3).!Using! the! same! data,! different! trajectories! of! BMI! development! from! adolescence! to! young! adulthood! (i.e.! trajectories! characterized! by! low! increases! in! BMI! and! trajectories! characterized! by! high! increases! in! BMI)! were! identified.! These! trajectories! were! also! not! differentially!associated!to!the!number!of!adverse!life!events!children!experienced!(chapter( 4).!Little!to!no!evidence!was!thus!found!for!a!relation!between!accumulation!of!adverse!life! events! and! BMI,! overweight! and! obesity! in! childhood! and! adolescence.! However,! associations!between!accumulation!of!adverse!life!events!and!BMI!were!identified!in!young! adulthood! (age! 22! years).! Adverse! events! in! different! life! phases,! shortly! as! well! as! long! before! young! adulthood,! were! associated! with! BMI! in! young! adulthood.! Accumulation! of! adverse! events! in! childhood! was! associated! with! a! higher! BMI! in! young! adulthood! and! accumulation! of! adverse! life! events! at! the! end! of! adolescence! and! beginning! of! young! adulthood!was!associated!with!a!lower!BMI!in!young!adulthood.!The!first!association!was! attributable! to! adverse! health! events,! such! as! illness! or! death! of! a! family! member! and! hospitalization,! while! the! second! association! was! attributable! to! adverse! relationship! and! victimhood!events,!such!as!conflicts!with!friends!or!family,!breakSups!and!being!a!victim!of! bullying!(chapter(3).!This!shows!that!the!direction!of!the!association!between!adverse!events! and!BMI!in!young!adulthood!may!depend!upon!the!type!of!experienced!adverse!events!and! the! life! phase! in! which! these! events! were! experienced.! It! also! shows! that! adverse! events! may!have!an!effect!on!BMI!development!long!after!their!occurrence.! The!second!research!question!was!whether!a!particularly!severe!adverse!childhood! event,!childhood!abuse,!was!associated!with!BMI!in!young!adulthood.!The!association!was! investigated!in!a!Dutch!sample!(chapter( 5)!and!in!a!nationally!representative!sample!from! the!United!States!(chapter(6).!Of!the!three!types!of!childhood!abuse!(i.e.!sexual,!physical!and! verbal!abuse),!only!sexual!abuse!was!related!to!BMI!in!Dutch!young!adult!females,!while!only! verbal! abuse! was! related! to! BMI! in! US! young! adult! females.! Associations! were! thus! only! identified!between!particular!types!of!childhood!abuse!and!BMI!in!young!adults!and!only!in! females.!Important!to!note!is!that!sexual!abuse!in!Dutch!females!was!not!only!associated! with!higher!BMI!at!the!beginning!of!young!adulthood,!but!also!with!a!higher!increase!in!BMI! in! young! adulthood.! This! again! shows! that! adverse! life! events! may! influence! BMI! development!long!after!their!occurrence.!!

The!third!research!question!of!this!dissertation!was!whether!the!association!between! childhood!abuse!and!BMI!in!young!adulthood!was!mediated!by!depression!and/or!anxiety! disorders.!The!identified!association!between!sexual!abuse!and!BMI!in!young!adult!females! was! partially! explained! by! diagnosis! of! major! depressive! disorder! (MDD)! before! young! adulthood,! but! not! by! diagnosis! of! generalized! anxiety! disorder! (GAD)! (chapter( 5).! The!

prevalence! of! MDD! before! young! adulthood! was! increased! in! males! and! females! who! experienced!childhood!abuse!and!the!occurrence!of!MDD,!in!turn,!was!related!to!a!higher! BMI!in!young!adult!females.!The!association!between!MDD!and!BMI!was!not!identified!in! males.!In!addition,!MDD!before!young!adulthood!was!not!related!to!higher!increases!in!BMI! in! young! adulthood,! neither! in! females! nor! in! males.! While! the! prevalence! of! GAD! was! increased!in!both!young!adult!females!and!young!adult!males!who!experienced!abuse,!GAD! was!not!associated!with!BMI!in!young!adults!of!either!sex.!GAD!thus!did!not!mediate!the! relation!between!childhood!abuse!and!BMI!in!young!adults.!

The! fourth! and! final! research! question! of! this! dissertation! was! whether! the! association! between! childhood! abuse! and! body! mass! index! in! young! adulthood! was! moderated! by! personality! traits.! Evidence! was! found! for! moderation! of! the! association! between!childhood!abuse!and!BMI!by!personality!traits!in!a!US!sample!(chapter(6).!AbuseS! and!personality!traitSspecific!effects!were!identified!in!males!and!females.!Low!extraversion! was! a! risk! factor! for! higher! BMI! in! verbally! abused! males! and! females.! Additionally,! in! physically!and!verbally!abused!females,!high!agreeableness!was!a!risk!factor!for!higher!BMI.! In! physically! abused! males,! in! turn,! high! conscientiousness! and! high! openness! were! risk! factors!for!higher!BMI.!Finally,!high!neuroticism!was!a!risk!factor!for!higher!BMI!in!sexually! abused!males.!Individuals!who!were!more!likely!to!experience!inner!distress!thus!seem!most! prone!to!BMI!changes!in!response!to!abuse.!

The! main! findings! of! this! dissertation! are! summarized! in! Figure! 1.! In! females,! accumulation! of! adverse! life! events! in! childhood! is! related! to! overweight! and! obesity! in! young!adulthood.!In!addition,!associations!are!identified!between!childhood!abuse!and!BMI! in!young!adult!females.!An!association!between!sexual!abuse!and!BMI!is!identified!in!Dutch! young! adult! females! and! between! verbal! abuse! and! BMI! in! US! young! adult! females.! The! relationship!between!sexual!abuse!and!BMI!in!Dutch!young!adult!females!is!partly!mediated! by!a!diagnosis!of!major!depressive!disorder!(MDD)!at!the!end!of!adolescence.!In!addition,! there! is! moderation! of! the! relationship! between! childhood! physical! and! verbal! abuse! and! BMI! by! personality! traits! in! young! adult! females.! ! In! males,! accumulation! of! adverse! life! events!in!childhood!is!related!to!overweight!and!obesity!in!young!adulthood.!No!associations! between!childhood!abuse!and!BMI!are!identified!in!young!adult!males.!However,!personality! traits!moderate!the!association!between!childhood!abuse!and!BMI!in!young!adult!males.!In! the!remainder!of!this!general!discussion,!I!will!reflect!on!the!identified!associations!and!on! explanations!for!why!certain!associations!were!not!identified.! ( ( (

! A.(Females( ! ! B.!Males! ! ! ! ( Figure(1.(Summary!of!the!findings!of!this!dissertation!(per!chapter)!for!females!(A)!and!males!(B).( ! YOUNG&ADULTHOOD& SEXUAL&ABUSE& ADVERSE&EVENTS& OVERWEIGHT/OBESITY& PHYSICAL&ABUSE& VERBAL&ABUSE& CHILDHOOD& BODY&MASS&INDEX& AGREEABLENESS& EXTRAVERSION& MAJOR&DEPRESSIVE& DISORDER&

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FACTORS(INFLUENCING(THE(ASSOCIATION(BETWEEN(ADVERSE(EVENTS(AND(BMI( The!associations!identified!in!the!first!decades!of!life!between!accumulation!of!adverse!life! events!and!overweight!measures!and!between!childhood!abuse!and!overweight!measures! were!few!in!number!and!small!in!size.!As!the!findings!exemplify,!this!could!be!caused!by!the! fact!that!the!association!between!adverse!life!events!and!BMI!is!influenced!by!the!presence! or!absence!of!other,!tertiary,!factors![5].!The!relation!between!adverse!life!events!and!BMI! could! be! influenced! by! child! characteristics,! life! phase! characteristics! and! event! characteristics!(Figure!2).!! ! ! Figure(2.!Factors!that!can!influence!the!association!between!adverse!life!events!and!body!mass!index! (BMI).! ! Child(characteristics(

Some! individuals! will! be! exposed! to! many! adverse! life! events! without! experiencing! detrimental!changes!to!their!BMI,!while!other!individuals!will!experience!BMI!changes!after! exposure! to! relatively! few! adverse! life! events! [3].! Differences! in! resilience! and! coping! between! individuals! are! considered! the! most! likely! explanation! to! underlie! differences! between!children!in!BMI!changes!following!adverse!life!events![3].!Resilience!and!coping!are! intertwined! concepts.! Resilience! is! “positive! adaptation! within! the! context! of! significant! adversity“! [6].! Coping! is! defined! as! “the! conscious! volitional! effort! to! regulate! emotion,! cognition,! behavior,! physiology,! and! the! environment! in! response! to! stressful! events! or! circumstances”! [7].! Children! with! high! resilience! and! effective! coping! strategies! may! not! experience!changes!in!BMI!in!response!to!the!occurrence!of!adverse!events,!while!children! with!low!resilience!and!ineffective!coping!strategies!may![3].!!

A!factor!related!to!coping!is!personality![8].!Personality!traits!are!enduring!patterns! of!thinking,!feeling!and!behavior!that!differ!between!people![9].!Personality!could!serve!both! as!a!factor!influencing!someone’s!appraisal!of!an!event!as!well!as!someone’s!response!to!an! event! [10].! The! relationship! between! various! types! of! childhood! abuse! and! BMI! was! influenced! by! specific! personality! traits! (chapter( 6).! Scoring! high! on! personality! traits! characterized! by! being! more! trusting! of! others,! more! orderly,! prone! to! distress! and! more! likely!to!keep!distressed!feelings!inside!was!shown!to!serve!as!a!risk!factor!for!higher!BMI! after!the!experience!of!abuse.!The!reverse!was!often!also!true:!the!same!type!of!abuse!was!

FACTORS(

I.(CHILD(CHARACTERISTICS( II.(LIFE(PHASE(CHARACTERISTICS( III.(EVENT(CHARACTERISTICS(

•  Personality, •  Health,behaviors, •  Weight,status, •  Brain,plas6city, •  Sex,hormone,levels, , •  Type, •  Dura6on, ,

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related!to!lower!BMI!in!participants!who!were!less!trusting!of!others,!less!orderly,!less!prone! to!distress!and!more!likely!to!express!distressed!feelings.!For!example,!verbal!abuse!was!not! only!related!to!higher!BMI!in!females!scoring!high!on!agreeableness,!but!was!also!related!to! lower! BMI! in! females! scoring! low! on! agreeableness.! Childhood! abuse! was! thus! related! to! increases!in!BMI!as!well!as!to!decreases!in!BMI,!depending!on!someone’s!personality.!In!line! with!this!finding,!childhood!abuse!has!been!related!to!overweight!and!binge!eating!as!well!as! to!underweight,!skipping!meals,!vomiting!and!other!eating!pathology!_{[11–14].!Accumulation!}

of! adverse! events! has! also! been! related! to! both! binge! eating! and! extreme! weight! control! behaviors!in!adolescents!and!young!adults![15].!Adverse!life!events!can!thus!be!related!to! higher!BMI!as!well!as!to!lower!BMI!and!the!direction!of!the!association!may!depend!upon! child!characteristics!such!as!personality.!

Other! child! characteristics! that! could! influence! the! presence! and! direction! of! an! association! between! adverse! life! events! and! BMI! are! dietary! intake,! physical! activity! and! weight!status.!Individuals!who!display!obesogenic!behaviors!and!have!a!high!weight!status! may!be!more!likely!to!increase!their!weight!when!stressed,!whereas!individuals!who!display! no! obesogenic! behaviors! and! have! a! normal! or! low! weight! status! may! be! more! likely! to! maintain! or! even! decrease! their! weight! when! stressed! [16,17].! Adverse! life! events! are! related!to!higher!BMI!in!children!who!have!high!sweet!food!intake,!but!not!in!children!with! low!intake!of!sweet!foods![18].!In!addition,!the!relationship!between!adverse!life!events!and! BMI!is!weaker!in!adolescents!with!high!physical!activity!levels!than!in!adolescents!with!low! physical!activity!levels![19].!The!idea!that!weight!status!may!influence!the!relation!between! adverse! events! and! changes! in! BMI! is! supported! by! a! study! in! adults! [20].! In! this! study,! weight!status!influenced!the!relation!between!the!impact!of!the!most!severe!experienced! event!and!changes!in!weight.!With!an!increase!in!the!reported!impact!of!the!adverse!event,! overweight! adults! showed! a! tendency! for! weight! gain,! while! adults! with! a! healthy! weight! showed!a!tendency!for!weight!reduction.!A!different!response!to!adverse!events!by!children! with! a! different! weight! status! is! also! a! possible! explanation! for! the! fact! that! we! did! not! observe!an!association!between!the!number!of!adverse!life!events!children!experienced!and! the!BMI!trajectories!identified!in!the!study!in!chapter(4((i.e.!the!‘normal!weight’,!‘early!onset! overweight’!and!‘late!onset!overweight’!trajectories).!When!adolescents!in!the!higher!BMI! trajectories!(the!‘early!onset!overweight’!and!the!‘late!onset!overweight’!trajectory)!respond! to! adverse! events! by! increasing! their! weight,! while! adolescents! in! the! ‘normal! weight’! trajectory! respond! to! adverse! events! by! maintaining! or! even! decreasing! their! weight,! no! relationship!between!accumulation!of!adverse!events!and!BMI!trajectory!will!be!identified.! Health! behavior! characteristics! and! weight! status! of! children! experiencing! adverse! events!

may!thus!influence!the!presence!and!direction!of!an!association!between!adverse!life!events! and!BMI.!!

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Life(phase(characteristics(

The! presence! and! direction! of! a! relation! between! adverse! events! and! BMI! could! also! be! influenced! by! the! examined! life! phase.! In! chapter( 3,! accumulation! of! adverse! events! in! childhood!was!related!to!higher!BMI!in!young!adulthood,!while!accumulation!of!adverse!life! events!in!adolescence!and!young!adulthood!was!related!to!lower!BMI!in!young!adulthood.! Childhood! may! thus! be! a! sensitive! period! for! stress! to! induce! elevations! in! BMI,! while! in! adolescence! stress! may! be! more! likely! to! have! BMI! lowering! effects.! Childhood! and! adolescence!are!different!stages!of!development,!biologically!as!well!as!psychologically,!and! this! could! cause! the! effect! of! events! on! body! and! behavior! to! be! different.! For! example,! different! brain! areas! are! most! vulnerable! to! outside! influences! in! different! phases! of! development![21].!Stress!in!early!childhood!has!greater!effects!on!the!hippocampus!than!on! the! prefrontal! cortex,! while! adolescent! stress! has! greater! effects! on! the! prefrontal! cortex! than!on!the!hippocampus![21–23].!These!differential!vulnerabilities!of!brain!areas!to!stress! in!different!life!phases!may!result!in!different!effects!of!stress!on!health!in!the!different!life! phases.!Another!biological!difference!between!adolescents!and!children!is!that!adolescents! are! exposed! to! higher! levels! of! circulating! sex! hormones! than! children.! Sex! hormones! influence! the! reactivity! of! the! hypothalamicSpituitarySadrenal! axis! (HPA! axis),! a! central! system! in! the! stress! response! [24].! The! higher! levels! of! sex! hormones! in! adolescence! compared! to! childhood! could! cause! differences! in! the! effects! of! stressors! on! HPA! axis! activity!in!the!different!life!phases![24].!In!addition,!brain!maturation!and!sex!hormones!can! influence! the! experience! of! stress! [25].! These! different! stress! experiences! in! response! to! adverse!events!in!the!different!life!phases!can!cause!differences!in!the!association!between! adverse!life!events!and!BMI.!In!conclusion,!differences!in!the!vulnerability!of!different!brain! areas! to! outside! influences,! in! the! effects! of! sex! hormones! on! the! HPA! axis! and! in! the! experience!of!stress!could!cause!the!association!between!adverse!life!events!and!BMI!to!be! different!in!childhood!and!adolescence.! ! Event(characteristics( Another!explanation!for!the!differences!in!the!association!between!accumulation!of!adverse! life!events!and!BMI!in!the!different!life!phases!could!be!that!in!our!study!different!events! were! measured! in! childhood! and! adolescence.! In! childhood,! a! limited! number! of! adverse! events!were!measured,!including!parental!illness,!parental!death,!parental!divorce!and!outS ofShome!placement.!At!the!end!of!adolescence!many!more!events!were!measured,!including! miscarriage,! conflicts! with! friends! or! family! and! unemployment.! Different! types! of! events!

!

can!have!different!effects.!Many!event!types!may!only!result!in!acute!stress![20].!However,! specifically!chronic!stress!is!believed!to!result!in!overweight!and!obesity![26].!Accumulation! of! adverse! events! would! be! assumed! to! reflect! chronic! rather! than! acute! stress! due! to! it! being! a! measure! of! subsequent,! repeated! exposure! to! stress! [27].! However,! when! many! minor! events! exerting! only! acute! stress! are! included,! accumulation! may! not! necessarily! reflect!chronic!stress![28].!Measurement!of!different!events!can!thus!lead!to!differences!in! the!association!between!accumulation!of!adverse!events!and!health.!This!idea!is!supported! by! the! fact! that! in! our! study! the! positive! association! between! accumulation! of! adverse! events!in!childhood!and!BMI!in!young!adulthood!was!attributable!to!adverse!health!events,! while! the! negative! association! between! accumulation! of! adverse! events! at! the! end! of! adolescence! and! BMI! in! young! adulthood! was! attributable! to! adverse! relationship! and! victimhood! events.! However,! while! in! our! study! adverse! health! events! were! measured! in! childhood,!adolescence!and!the!beginning!of!young!adulthood,!only!adverse!health!events!in! childhood!were!associated!with!BMI.!In!addition,!in!our!study!similar!adverse!events!were! measured!both!at!the!start!and!at!the!end!of!adolescence!and!only!the!latter!were!related!to! BMI.!Measurement!of!different!adverse!events!in!the!different!life!phases!does!thus!not!fully! explain!the!differences!in!the!identified!relations.!Moreover,!if!the!type!of!event!would!be! crucial!for!the!existence!of!a!relation!between!adverse!events!and!BMI,!one!would!expect! childhood! abuse,! one! of! the! most! severe! adverse! events,! to! be! related! to! BMI! [28].! In! contrast,! we! identified! few! associations! between! childhood! abuse! and! BMI! in! young! adulthood!(chapter(5!and!chapter(6).!! In!this!dissertation,!the!relation!between!various!types!of!childhood!abuse!and!BMI!in! young!adulthood!was!examined.!While!only!a!relation!between!sexual!abuse!and!BMI!was! identified!in!young!adult!females!in!a!Dutch!cohort!(chapter(5),!only!an!association!between! verbal!abuse!and!BMI!was!identified!in!young!adult!females!in!a!nationally!representative! sample!from!the!United!States!(chapter(6).!Differences!in!the!results!of!both!studies!could! be!caused!by!the!fact!that!the!data!came!from!different!countries,!with!highly!differing!living! conditions,! policies! and! healthScare! systems.! Differences! could! also! be! caused! by! the! fact! that! the! sample! from! the! US! was! several! years! older! than! the! Dutch! sample.! In! addition,! differences! could! be! caused! by! the! fact! in! the! two! studies! different! tools! were! used! to! measure!abuse.!In!the!US!study!(chapter(6),!abuse!was!measured!by!one!question!assessing! only!severe!abuse,!while!in!the!Dutch!study!(chapter( 5)!multiple!questions,!also!assessing! less! severe! forms! of! abuse,! were! used.! It! is! thus! possible! that! the! measures! used! for! childhood!abuse!contain!abuse!experiences!that!do!not!all!have!an!equally!large!impact.!The! fact! that,! in! chapter( 5,! one! or! more! occurrences! of! verbal! abuse! were! reported! by! about! 75%!of!the!sample,!an!extremely!high!percentage,!supports!this!idea.!It!may!be!that!only!the!

less! common,! and! presumably! more! severe,! forms! of! verbal! abuse,! such! as! threatening! a! child,!are!related!to!BMI![29].!

Another!event!characteristic!that!could!influence!the!relation!between!adverse!life! events! and! BMI! is! the! duration! of! adverse! events! [30,31].! The! longer! the! duration! of! an! adverse!event,!the!more!likely!an!event!is!to!exert!chronic!stress!rather!than!acute!stress! and! hence! BMI! changes.! For! example,! a! conflict! with! family! or! friends! can! be! quickly! resolved!or!can!be!drawnSout.!When!a!conflict!is!quickly!resolved,!the!conflict!is!most!likely! to! result! in! acute! stress! only,! while! it! is! more! likely! to! result! in! chronic! stress! when! the! conflict!is!drawnSout.!Previous!studies!showed!that!individuals!that!needed!a!longer!time!to! process! the! events! they! experienced! and! individuals! that! experienced! events! at! multiple! time!points!had!a!lower!physical!health!and!were!more!likely!to!be!overweight![32,33].!The! time! someone! is! exposed! to! events! may! thus! influence! the! relation! between! adverse! life! events!and!physical!health.!The!type!of!adverse!events!measured!and!the!duration!of!the! measured! adverse! events! could! thus! explain! why! different! associations! between! accumulation!of!adverse!life!events!and!BMI!were!identified!in!the!different!life!phases.! (

DELAY(IN(THE(EFFECT(OF(ADVERSE(EVENTS(ON(BMI((

In!both!studies!on!accumulation!of!adverse!life!events!and!studies!on!childhood!abuse!in!this! dissertation,!associations!with!BMI!changes!were!primarily!found!at!the!end!of!adolescence! and! in! young! adulthood.! A! study! examining! differences! in! obesity! rates! between! sexually! abused! females! and! nonSsexually! abused! females! in! childhood! and! young! adulthood! similarly!only!identified!a!difference!in!young!adulthood!as!a!result!of!a!higher!increase!in! BMI!between!childhood!and!young!adulthood!in!sexually!abused!females![34].!In!addition,!in! a!metaSanalysis!on!childhood!abuse!and!obesity,!an!association!was!identified!with!obesity! in!adulthood,!but!not!with!obesity!in!childhood!and!adolescence![35].!A!likely!explanation!for! these! findings! is! that! there! is! a! delay! in! the! effects! of! childhood! abuse! on! BMI.! This! dissertation!suggests!that!some!associations!between!childhood!abuse!and!BMI!(have)!come! to! expression! in! young! adults.! This! is! in! line! with! previous! studies! identifying! no! or! few! associations!in!young!adults![36,37].! ! There!may!be!a!time!lag!between!the!occurrence!of!adverse!life!events!and!changes! in!BMI,!because!of!the!time!it!takes!for!intermediary!processes!to!take!place.!As!mentioned! in!the!introduction,!psychosocial!stressors!are!assumed!to!affect!BMI!via!two!mechanisms:! via!health!behaviors!and!via!the!body’s!biology![26,38].!Obviously,!when! health!behaviors! are!affected,!this!does!not!result!in!immediate!changes!in!BMI.!Moreover,!health!behaviors! in! childhood! may! not! be! influenced! at! all,! because! of! the! strong! influence! of! parents! on! children’s!health!behaviors![39].!However,!as!children!become!adolescents!and!young!adults! their! health! behaviors! may! be! influenced! by! adverse! events.! This! is! because! in! these! life!

phases!health!behaviors!increasingly!come!under!their!own!control!and!responsibility![39].! Adolescence!and!young!adulthood!may!thus!be!the!life!phases!in!which!adverse!childhood! events!come!to!expression!via!alterations!in!health!behaviors.!However,!even!this!will!not! immediately!result!in!changes!in!BMI.!If!psychosocial!stressors!influence!BMI!via!an!effect!on! health!behaviors,!an!association!with!BMI!is!probably!not!seen!until!adulthood.!!

When! psychosocial! stressors! exert! an! effect! on! BMI! via! alterations! in! biological! reactions!in!the!body,!a!time!lag!between!event!exposure!and!BMI!changes!is!also!likely!to! exist.! For! example,! hippocampal! volume! changes! in! response! to! childhood! stress! are! generally!not!observed!in!childhood,!but!are!shown!in!adulthood![31].!There!can!thus!be!a! long!lag!before!biological!alterations!in!response!to!adverse!events!come!to!expression!and! translate! into! adverse! health! [40].! If! psychosocial! stressors! influence! BMI! via! an! effect! on! biological!reactions,!effects!may!thus!not!be!seen!until!adulthood.! Finally,!when!the!relation!between!adverse!events!and!changes!in!BMI!is!dependent! upon!other,!intermediary,!health!conditions,!a!time!lag!between!both!factors!is!also!likely!to! exist.!In!this!dissertation,!depression!and!anxiety!disorders!were!considered!as!intermediate! health!conditions!that!could!connect!adverse!life!events!to!changes!in!BMI.!! ! THE(ROLE(OF(DEPRESSION(IN(THE(RELATION(BETWEEN(ADVERSE(EVENTS(AND(BMI(

In! the! study! described! in! chapter( 5,! a! rise! in! major! depressive! disorder! (MDD)! and! generalized!anxiety!disorder!(GAD)!rates!following!the!occurrence!of!childhood!abuse!was! noted.!The!occurrence!of!GAD!was!not!related!to!BMI!in!young!adulthood.!The!occurrence!of! MDD!was!also!not!related!to!BMI!in!young!adult!males.!However,!the!occurrence!of!MDD! before!young!adulthood!was!related!to!higher!BMI!at!the!beginning!of!young!adulthood!in! females.! The! relation! between! childhood! sexual! abuse! and! BMI! in! females! was! partially! explained!by!the!occurrence!of!MDD.!It!is!important!to!note,!however,!that!the!possibility!of! reverse!causation!in!the!relation!between!MDD!and!BMI!cannot!be!completely!ruled!out.!It! is!possible!that!instead!of!MDD!before!young!adulthood!contributing!to!a!higher!BMI!at!the! beginning! of! young! adulthood,! a! higher! BMI! in! childhood! or! adolescence! actually! contributed!to!the!development!of!MDD!before!young!adulthood![41].!!

'

Mediation(of(the(relation(between(childhood(abuse(and(BMI(by(MDD(

Depression! and! BMI! may! be! associated! via! the! same! two! mechanisms! that! were! also! mentioned!to!explain!the!association!between!adverse!events!and!BMI.!Firstly,!they!may!be! associated!via!unhealthy!behaviors![42].!For!example,!depression!has!been!associated!with! emotional!eating!(e.g.!eating!in!response!to!negative!emotions)![43,44]!and!emotional!eating! has! been! associated! with! higher! unhealthy! dietary! intake! [45,46]! and! higher! BMI! [43,44,46,47].! Here,! emotional! eating! serves! as! a! mediator! of! the! relation! between!

depression!and!BMI![43,44].!Depression!has!also!been!related!to!lower!physical!activity!and! lower!physical!activity!selfSefficacy![44,48].!Lower!physical!activity!and!lower!physical!activity! selfSefficacy,! in! turn,! have! been! related! to! increased! adiposity! and! BMI! [44,48].! Physical! activity! and! physical! activity! selfSefficacy! also! serve! as! mediators! of! the! relation! between! depression! and! BMI! [44,48].! Thus,! unhealthy! behaviors! may! serve! as! a! mechanism! connecting!depression!to!BMI.!

A!second!explanation!for!the!association!between!depression!and!BMI!may!be!that! the!conditions!are!biologically!related.!Dysregulation!of!the!HPA!axis,!a!system!of!biological! reactions!in!the!body!that!plays!a!central!role!in!the!stress!response,!has!been!implicated!in! both! obesity! and! depression! [49].! Altered! activity! of! the! HPA! axis! has! been! shown! in! depressed!patients![49]!and!cortisol,!the!end!product!of!the!HPA!axis,!is!suggested!to!lead!to! increased!unhealthy!food!intake!and!fat!deposition!in!the!body![17,50,51].!Depression!and! obesity!may!thus!be!related!via!alterations!in!biological!reactions!in!the!body.!

On!the!preceding!pages,!several!mechanisms!have!been!described!that!are!suggested! in! the! literature! to! connect! adverse! events! and! BMI.! In! Figure! 3,! a! graphical! summary! of! these! mechanisms! is! given.! Adverse! events! may! be! related! to! BMI! via! changes! in! health! behaviors!and!biological!reactions!in!the!body.!Adverse!events!can!also!be!associated!with! BMI!via!mental!health!conditions.!Mental!health!conditions!and!BMI!may!be!associated!via! changes!in!health!behaviors!and!biological!reactions.!! ! ! ' ADVERSE'EVENTS' CHILDHOOD' ADULTHOOD' HEALTH'BEHAVIORS' MENTAL'HEALTH' BIOLOGICAL'REACTIONS' BODY'MASS'INDEX' EXPOSURE' INTERMEDIARY' PROCESSES'AND' FACTORS' OUTCOME' Figure(3.!Graphical!summary!of!proposed!relation!between!adverse!life!events!and!body!mass!index! (BMI).!Note:!(1)!moderating!factors!are!not!displayed!in!this!figure!and!(2)!the!timeline!in!this!figure! provides!an!indication!of!the!timing!of!the!different!elements!in!the!framework,!but!timing!may!vary! across!individuals.!!

!

Moderation(of(the(relation(between(MDD(and(BMI(by(childhood(abuse(

Next!to!evidence!for!mediation!of!the!relation!between!childhood!sexual!abuse!and!BMI!by! MDD,! we! also! found! evidence! for! moderation! of! the! relation! between! MDD! and! BMI! by! childhood!sexual!abuse.!In!females!who!experienced!childhood!sexual!abuse,!MDD!and!BMI! were!associated,!while!no!evidence!for!an!association!was!identified!in!females!who!did!not! experience!childhood!sexual!abuse.!As!mentioned!before,!dysregulation!of!the!HPA!axis!has! been!implicated!in!both!obesity!and!depression![49].!In!addition,!dysregulation!of!the!HPA! axis!has!been!suggested!to!be!a!consequence!of!childhood!abuse![52].!MDD!and!changes!in! BMI! may! thus! be! the! result! of! related! alterations! in! biological! reactions! in! the! body! in! response!to!childhood!abuse![38,42].!The!biological!profile!of!MDD!and!obesity!in!response! to! childhood! abuse! may! therefore! be! different! from! the! biological! profile! of! MDD! and! obesity!arising!from!different!causes.!In!line!with!this!idea,!MDD!in!response!to!childhood! abuse! has! been! shown! to! differ! biologically! from! MDD! from! other! causes! [53].! Research! found!that!individuals!who!experienced!childhood!abuse!and!who!suffered!from!depression! had! a! smaller! hippocampal! volume,! higher! inflammatory! biomarkers! and! a! higher! stress! response!than!depressed!individuals!who!did!not!experience!childhood!abuse![54–58].!This! biological!profile!of!depression!in!response!to!childhood!abuse!may!also!be!associated!with! changes!in!BMI.!The!relation!between!MDD!and!BMI,!presented!in!Figure!2,!may!therefore! be!specifically!present!in!individuals!who!experienced!childhood!abuse.! ( GENDER(DIFFERENCES( Several!associations!in!this!dissertation!were!identified!among!women,!but!not!among!men.! Previous!research!also!only!detected!associations!between!childhood!abuse!and!obesity!in! females,!more!readily!detected!associations!in!females!or!detected!stronger!associations!in! females![35,37,59].!!

Gender! differences! in! the! association! between! childhood! abuse! and! BMI! may! be! explained!by!differences!in!health!behaviors!between!the!sexes.!Women!are!shown!to!score! higher! than! men! on! emotional! eating! and! stressSrelated! eating! and! lower! than! men! on! physical!activity!selfSefficacy![44,60].!These!health!behaviors!and!beliefs!about!the!ability!to! perform! health! behaviors! are! suggested! to! mediate! the! relation! between! adverse! events! and!BMI.!Therefore,!the!relation!between!adverse!events!and!BMI!may!be!more!pronounced! in!women!than!in!men.!! Gender!differences!in!the!association!between!depression!and!BMI!may!also!explain! differences!in!the!association!between!childhood!abuse!and!BMI.!Depression!is!more!often! associated!with!weight!gain!in!women!than!in!men![61].!This!may!be!due!to!differences!in! health!behaviors!between!women!and!men!with!depression.!Depression!is!associated!with!

emotional! eating! [43,44]! and! an! association! between! emotional! eating! and! unhealthy! dietary! intake! has! been! identified! in! females! with! depression,! but! not! in! males! with! depression! [45].! Therefore,! depression! could! be! specifically! related! to! a! higher! BMI! via! emotional! eating! and! unhealthy! dietary! intake! in! women.! A! stronger! relation! between! depression!and!BMI!in!females!may!explain!why!associations!between!childhood!abuse!and! BMI!are!detected!in!young!adult!females,!but!not!in!young!adult!males.!

Besides!via!health!behaviors!and!health!conditions,!adverse!events!and!BMI!may!also! be! related! via! biological! reactions.! Biological! differences! between! the! sexes! in! brain! maturation! and! functioning! during! childhood! and! adolescence! may! lead! to! gender! differences! in! the! appraisal! of! events! in! these! life! phases! [25].! In! addition,! differences! between! the! sexes! in! the! timing! of! puberty! onset,! in! the! effect! of! sex! hormones! on! the! stress!response!and!in!interactions!of!sex!hormones!with!stress!on!brain!development!could! serve!as!explanations!for!why!the!relationship!between!childhood!abuse!and!BMI!is!different! for!women!and!men![62].!In!line!with!the!idea!of!puberty!and!sex!hormones!influencing!the! reaction! to! stress,! gender! differences! in! functioning! of! the! HPA! axis! seem! to! emerge! in! adolescence![25].!Female!sex!hormones!are!suggested!to!particularly!influence!the!HPA!axis! [25].!Therefore,!the!relation!between!adverse!life!events!and!BMI!may!be!more!pronounced! in!women.!Differences!in!health!behaviors!and!biology!between!the!sexes!may!thus!explain! why!childhood!abuse!is!related!to!BMI!in!women,!but!not!in!men.!! ( STRATEGIES(TO(PREVENT(CHANGES(IN(BMI(IN(RESPONSE(TO(ADVERSE(EVENTS(( To!my!knowledge,!no!studies!into!prevention!of!obesity!following!the!experience!of!adverse! events!have!been!performed.!However,!cohort!studies!and!intervention!studies!to!reduce! depression!and!depressive!symptoms!in!response!to!adverse!events!provide!suggestions!for! obesity! prevention! strategies! following! adverse! events.! As! depression! and! BMI! changes! following!childhood!abuse!are!related,!strategies!to!prevent!depression!following!childhood! abuse! may! also! prevent! changes! in! BMI.! Ideally! of! course,! adverse! events! in! childhood,! especially!severe!events!causing!high!levels!of!stress,!should!be!prevented![63].!However,!if! prevention!of!these!adverse!events!is!not!possible,!preventing!health!problems!associated! with!adverse!events!holds!a!higher!promise!and!is!likely!more!costSeffective!than!treatment! of!health!problems!later!in!life![63,64].!In!all!these!efforts,!the!possible!cause!of!the!health! problems! needs! to! be! taken! into! account.! Prevention! efforts! aimed! at! MDD! need! to! be! different!when!MDD!is!the!result!of!childhood!abuse!than!when!MDD!has!a!different!cause,! as!the!clinical!course!of!and!treatment!success!in!MDD!is!influenced!by!adverse!childhood! experiences![53,65,66].!Obesity!prevention!strategies!for!children!who!experienced!adverse! events! may! therefore! also! need! to! have! a! different! content! than! overweight! and! obesity! prevention!strategies!in!general![38].!Studies!suggest!that!increasing!acceptance!of!negative!

!

emotions,!resilience,!engagement!in!health!behaviors,!effective!family!functioning!and!social! support!are!all!promising!strategies!to!reduce!adverse!health!outcomes!in!individuals!who! experienced!adverse!life!events.!In!addition,!changing!DNA!methylation!patterns!may!be!a! biological! strategy! to! reduce! depression! and! changes! in! BMI! following! the! experience! of! adverse!events!(Figure!4).!Below,!all!these!factors!will!be!discussed!in!more!detail.! ! ! ! Figure(4.!Factors!that!can!be!targeted!in!overweight!and!obesity!prevention!programs!following!the! experience!of!adverse!events.! ! Factors(to(target(in(intervention(programs(

Firstly,! child! characteristics! can! be! targeted! in! prevention! and! intervention! programs! to! reduce!adverse!health!conditions!in!response!to!adverse!events.!This!dissertation!shows!that! personality! traits! can! be! a! fruitful! target! for! obesity! prevention! strategies! after! the! experience!of!adverse!events.!For!example,!increasing!extraversion!could!prevent!increases! in!BMI!in!verbally!abused!children!low!on!extraversion.!Increasing!children’s!acceptance!(as! opposed!to!children’s!avoidance)!of!negative!emotions!may!also!result!in!better!mental!and! physical!health!following!adverse!events.! Individuals!who!were!more!accepting!of!negative! emotions! did! not! experience! an! increase! in! depressive! symptoms! in! reaction! to! adverse! events,! whereas! individuals! who! were! less! accepting! of! negative! emotions! did! show! increases! in! depressive! symptoms! in! response! to! adverse! events! [67].! In! addition,! the! experience!of!adverse!events!is!related!to!a!lower!depression!score!in!individuals!who!score! higher!on!resilience!than!in!individuals!who!score!lower!on!resilience![68].! Physical!activity! levels! were! also! increased! by! an! intervention! to! increase! resilience! and! health! behaviors,! pointing!to!a!possible!physical!health!benefit!of!increasing!resilience!as!well![69].!!

Not!only!factors!related!to!the!child!can!be!targeted,!but!the!social!environment!of! children!who!experienced!adverse!events!can!also!be!targeted!to!decrease!adverse!effects! on! health.! Factors! such! as! family! dysfunction! and! social! support! are! important.! Programs! that! increase! children’s! exposure! to! safe,! stable! and! nurturing! environments! and! relationships! by! providing! assistance! to! parents,! in! terms! of! social! support! and! teaching! them! responsible! health! behaviors! and! childSrearing! and! management! skills,! have! been! shown! to! reduce! children’s! exposure! to! adversity! and! improve! children’s! cognitive! and!

FACTORS(

I.(CHILD(CHARACTERISTICS( II.(SOCIAL(ENVIRONMENT( III.(BIOLOGY(

•  Personality, •  Coping, •  Resilience, •  Health,behaviors, •  Family,func:oning, •  Social,support,, •  DNA,methyla:on,

socialSemotional!development![64].!In!addition,!changes!in!HPA!axis!activity!were!not!seen!in! children! in! foster! care! that! participated! in! an! intervention! aimed! at! stimulating! a! warm! environment,! positive! behavior! and! social! and! developmental! competencies,! while! they! were!seen!in!children!in!foster!care!that!did!not!receive!the!intervention![70].!In!line!with! stimulating!a!warm!environment,!social!support!could!be!an!important!factor!to!increase!in! children! who! experienced! adverse! events! [71].! Adults! who! experienced! childhood! maltreatment!and!were!diagnosed!with!a!mental!disorder!less!often!reported!participation! in!sports!clubs,!having!had!friends!and!the!presence!of!a!support!figure!outside!the!home!in! childhood!than!adults!who!were!maltreated!as!children,!but!who!were!not!diagnosed!with!a! mental!disorder![71].!!

A! potential! biological! target! in! prevention! and! intervention! programs! is! DNA! methylation.!Differences!in!susceptibility!to!depression!after!trauma!exposure!may!be!traced! back! to! differences! in! DNA! methylation! following! trauma! exposure! [72].! DNA! methylation! can! cause! soScalled! silencing! of! genes:! genes! cannot! be! transcribed! and! translated! into! proteins,! because! of! alterations! (i.e.! the! addition! of! methyl! groups)! made! to! the! DNA! structure.! These! different! DNA! methylation! and! gene! expression! patterns! may! result! in! altered!biological!processes!in!the!body!following!childhood!abuse,!such!as!an!altered!stress! response![73]!and!reflect!the!risk!of!developing!MDD!following!childhood!abuse![72].!These! DNA! methylation! patterns! may! additionally! reflect! the! risk! of! developing! BMI! changes! following! childhood! abuse.! Targeting! DNA! methylation! profiles! using! pharmaceutical! or! nutritional! interventions! may! therefore! be! a! promising! route! to! prevent! depression! and! obesity!following!adverse!events![72].!Future!studies!should!examine!whether!this!approach! is! safe! and! indeed! results! in! reduced! rates! of! depression! and! obesity! following! adverse! events.!

!

Timing(of(interventions(

For! most! interventions,! the! optimal! time! frame! would! be! childhood! or,! at! the! latest,! adolescence.! Childhood! and! adolescence! are! periods! of! increased! brain! plasticity! [74].! In! these!time!periods,!the!brain!is!especially!vulnerable!to!exposures!that!can!cause!alterations,! such!as!stressors![74].!Therefore!these!periods!may!also!be!the!best!periods!to!reverse!the! effect!of!stressors.!In!addition,!the!fact!that!MDD!and!GAD!rates!in!response!to!childhood! abuse!are!already!elevated!in!adolescence!(chapter(5)!and!the!fact!that!it!is!more!difficult!to! reverse!adverse!health!behavior!patterns!once!they!are!established!warrants!prevention!and! intervention!efforts!as!early!as!possible![63].! ( ( (

!

METHODOLOGICAL(CONSIDERATIONS(IN(ACCUMULATION(OF(ADVERSE(EVENTS(RESEARCH( There! are! several! methodological! considerations! when! performing! studies! on! the! accumulation! of! adverse! events.! One! inherent! limitation! of! studies! on! accumulation! of! adverse!events!is!the!lack!of!a!universally!accepted!method!for!measuring!adverse!events! and! constructing! an! accumulated! adverse! events! measure.! Results! of! existing! studies! assessing!the!association!between!accumulated!adverse!events!and!overweight,!obesity!and! BMI! in! childhood! are! heterogeneous! (chapter( 2).! Differences! in! the! methods! used! to! measure! adverse! events! and! to! construct! an! accumulated! adverse! events! measure! likely! partially! explain! these! differences.! While! studies! often! use! some! type! of! sum! score,! the! included!adverse!events,!the!way!information!on!these!adverse!events!is!generated!and!the! way!in!which!sum!scores!are!created!differ!strongly!between!studies.!Below,!I!will!first!focus! on! aspects! to! consider! when! measuring! adverse! events! and! I! will! subsequently! focus! on! aspects!to!consider!when!constructing!an!adverse!events!score.!

!

Measuring(accumulation(of(adverse(events(

There!are!several!measurement!aspects!to!carefully!consider!when!studying!accumulation!of! adverse! events.! Firstly,! to! truly! study! accumulation! of! adverse! events,! measurement! of! a! large!number!of!different!types!of!events!is!advisable.!When!studying!only!a!small!number!of! events,!results!can!be!driven!by!the!presence!or!absence!of!a!particular!event!rather!than!by! accumulation!of!events.!Further,!if!a!limited!range!of!event!types!is!included!in!the!adverse! events!score,!one!is!examining!adverse!events!experienced!in!a!certain!domain,!rather!than! accumulation!of!adverse!events!in!general.!To!exclude!the!possibility!that!events!in!a!certain! domain! drive! associations,! researchers! can! create! sum! scores! of! the! different! types! of! adverse! events! in! addition! to! creating! an! overall! adverse! event! score.! The! association! between!these!different!accumulated!adverse!events!scores!and!overweight,!obesity!or!BMI! can!subsequently!be!determined,!as!we!did!in!chapter(3(and(chapter(4.!!

A! second! aspect! to! consider! when! measuring! adverse! events! is! the! length! of! the! recall!period.!The!period!over!which!adverse!events!are!recalled!should!be!long!enough!for! measures! to! truly! reflect! which! individuals! experienced! more! adverse! events! and! which! individuals!experienced!fewer!adverse!events.!In!addition,!the!recall!period!should!be!long! enough! for! changes! in! overweight,! obesity! or! BMI! to! become! apparent.! The! recall! period! should,! however,! not! be! too! long! either.! The! length! of! the! recall! period! should! not! raise! questions!about!whether!adequate!and!reliable!recall!of!adverse!events!is!possible.!

A!third!aspect!to!consider!when!measuring!accumulation!of!adverse!events!is!which! informant!to!use.!As!the!child!is!the!most!likely!informant!to!know!exactly!which!events!it! encountered,!the!child!is!the!best!informant!to!report!on!adverse!life!events!in!its!own!life,!if!

age!permits![75].!Only!if!the!child!is!too!young!or!the!period!studied!is!a!period!of!which!the! child!has!no!conscious!recollection,!someone!close!to!the!child!should!report!on!the!adverse! events!the!child!has!experienced.!!

A! final! important! aspect! to! consider! when! measuring! adverse! events! is! which! measurement! method! to! use.! Information! on! adverse! events! can! be! collected! in! an! interview! or! by! using! a! selfSadministered! questionnaire.! In! interviews,! information! can! be! collected!on!a!more!complete!set!of!events!than!can!be!done!through!most!questionnaires! [75].! However,! the! downside! of! interviewing! is! that! individuals! may! not! mention! adverse! events!for!which!they!feel!embarrassment![75].!Nonetheless,!using!an!interview!serves!the! advantage!of!being!better!able!to!judge!the!reliability,!the!context!and!the!exact!content!of! the!reported!adverse!events!than!can!be!done!using!a!questionnaire![75].!When!possible,! the!use!of!an!interview!is!therefore!advised.!! ! Construction(of(an(accumulated(adverse(event(measure( With!regard!to!the!construction!of!the!accumulated!adverse!events!measure,!two!aspects! should!be!considered.!The!first!aspect!is!whether!to!use!a!continuous!accumulated!adverse! events!measure!or!to!apply!cutSoffs!and!use!a!categorical!accumulated!adverse!childhood! events! measure! with! a! limited! number! of! categories.! Creating! an! accumulated! adverse! events!measure!with!a!limited!number!of!categories!by!applying!cutSoffs!is!discouraged![76].! In!our!systematic!review!and!metaSanalysis,!results!of!studies!on!accumulation!of!adverse! events! and! overweight! in! childhood! that! used! a! categorical! accumulated! adverse! events! measure!were!heterogeneous,!while!results!of!studies!that!used!a!continuous!accumulated! adverse!events!measure!were!not!heterogeneous!(chapter( 2).!Contrasting!individuals!who! experienced!high!and!low!numbers!of!adverse!events!may!indeed!result!in!the!identification! of!larger!associations!with!health,!but!there!likely!is!considerable!variability!in!the!exposure! within!the!contrasted!groups![76].!Therefore,!the!clinical!relevance!of!these!contrasts!and! the!usefulness!of!the!results!in!daily!practice!can!be!questioned.!Children!who!experienced!a! certain! threshold! of! adverse! events! cannot! easily! be! identified! and! prevention! strategies! aimed! at! these! children! are! difficult! to! implement.! The! use! of! a! continuous! adverse! childhood!events!measure!is!advised![76].!!

The! second! aspect! to! consider! with! regard! to! the! construction! of! the! accumulated! adverse!events!measure!is!whether!or!not!to!weigh!the!experienced!adverse!events!based! on!their!severity.!Using!a!severity!rating,!based!on!reports!of!the!person!who!experienced! the!adverse!events,!could!be!crucial!for!the!identification!of!a!relationship!between!adverse! life!events!and!BMI!as!the!experienced!severity!may!mimic!one’s!physiological!reaction!or! may!influence!one’s!behavioral!reaction!to!adverse!events![77].!However,!a!study!examining! the! relation! between! a! combination! measure! of! the! number! of! experienced! adverse! life!

!

events,! the! severity! of! the! events! and! chronicity! of! the! events! did! not! show! a! relation! between!this!measure!and!BMI![77].!In!addition,!an!overall!score!of!motherSreported!impact! of!adverse!events!was!not!related!to!overweight!in!adolescents![33].!Whether!measures!of! accumulated!adverse!events!that!include!a!severity!rating!serve!as!a!better!predictor!of!BMI! is!thus!debatable,!definitely!if!the!severity!rating!is!not!made!by!the!respondent.!In!addition,! researchers! should! consider! the! possibility! that! factors! moderating! the! relation! between! adverse! life! events! and! BMI,! such! as! personality,! can! influence! the! severity! rating! of! the! respondent.!Moderators!may!thus!not!be!identified!when!a!severity!rating!is!applied.!When! one!truly!wants!to!study!the!relationship!between!accumulation!of!adverse!events!and!BMI,! without!attenuating!the!effect!of!moderating!factors,!a!severity!rating!should!therefore!not! be!used!in!the!accumulated!adverse!life!events!measure.!!!! ! CONCLUSION(

This! dissertation! shows! that! accumulation! of! adverse! life! events! in! childhood! and! adolescence!is!related!to!BMI!in!young!adulthood,!while!it!is!not!related!to!BMI!in!childhood! and!adolescence.!In!addition,!childhood!abuse!has!few!associations!with!initial!BMI!in!young! adulthood!and!is!most!strongly!associated!with!increases!in!BMI!in!young!adulthood.!These! last!associations!are!genderSspecific:!they!are!identified!in!females,!but!not!in!males.!There! thus!likely!is!a!delay!in!the!effect!of!adverse!life!events!in!childhood!on!BMI.!In!addition,!the! association!is!more!pronounced!in!females!than!in!males.!If!adverse!life!events!indeed!get! under!the!skin!at!an!early!age!and!slumber!there!for!years!before!they!come!to!expression!as! serious! health! conditions,! targeting! children! is! crucial! for! prevention! of! these! conditions.! Prevention!and!intervention!efforts!aimed!at!reducing!overweight!and!obesity!development! in!response!to!adverse!life!events!would!benefit!from!a!better!understanding!of!child!and! event! characteristics! that! influence! the! relation! between! adverse! life! events! and! BMI! and! from!a!better!biological!understanding!of!the!relation.!!

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