Intergenerasjonell overføring av personlighet og

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Intergenerasjonell overføring av personlighet og psykiske lidelser: en gjenganger

Eivind Ystrøm

Avdeling for psykiske lidelser, Folkehelseinstituttet Psykologisk institutt, Universitetet i Oslo

Farmasøytisk institutt, Universitetet i Oslo

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Foreldre

Barn

Latent risiko

g

a

p

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Genetikk

Kvantitativ genetikk (1921)

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Hva er heritabilitet

• ”Andelen av observerbare forskjeller mellom individer som forklares av genetiske ulikheter innenfor en bestemt befolkning”.

• Heritabilitet er forholdet mellom to varianser

• Genetisk varians / total varians

• Andel, prosent, av total varians som skyldes genetiske forskjeller.

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Minnesota Twins reared apart

Bouchard, T. J., Lykken, D. T., McGue, M., Segal, N. L., &

Tellegen, A. (1990).

Sources of human psychological differences: The Minnesota study of twins reared apart.

Science, 250(4978), 223-228.

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Alle tvillingstudier samlet

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Eric Turkheimer: The three laws of behavior genetics

1. All human traits are heritable.

2. The effect of being raised in the same family is smaller than the effect of genes.

3. A substantial proportion of the variation in complex human

behavioral traits is not accounted for by the effects of genes or families.

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Om alle trekk og psykiske lidelser er arvbare…

• Om all variasjon i menneskelig atferd, følelser og kognisjoner gjenspeiler genetisk variasjon, så:

• Må man alltid ta stilling til

genetikk i en intergenerasjonell

observasjonsstudie. ^Foreldre

Barn

Latent risiko

g

a

p

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Intergenerational transmission of risk (IToR)

• Folkehelseinstituttet: Line Gjerde (postdoc), Espen Eilertsen (PhD), Ragnhild Ørstavik, Gunn Peggy Knudsen, Ted Reichborn-Kjennerud, Eivind Ystrøm (PI)

• UiO, psykologisk inst.: Espen Røysamb, Nikolai Czajkowski

• Atferdssenteret: Henrik D. Zachrisson, Imac Zambrana

• Boston College: Eric Dearing

• Harvard / Smith College: Kathleen McCartney

• King's College, Inst. of psych.: Tom McAdams (postdoc), Fruhling Rijkdijk, Thalia Eley

• Virginia Commonwealth Univ.: Kenneth S. Kendler

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Intergenerational

transmission of risk (IToR)

• Hvordan psykiske lidelser og temperament overføres i familier.

• Foreldrene:

• Angst, depresjon, alkoholmisbruk og ADHD.

• Barna:

• Temperament, internaliserende vansker, eksternaliserende vansker og ADHD.

• FRIMEDBIO unge forskertalenter 2014-2017.

• Postdoc: Line Gjerde

• PhD: Espen Eilertsen

• Welcome Trust 2015-2020.

• Postdoc for Tom McAdams.

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IToR

• Den norske mor og barn studien

• Ca 110 000 svangerskap 1999-2008

• Foreldrene

• Ca 30 000 personer som er hel og halvsøsken

• Ca 500 tvillinger

• Barna

• Ca 30 000 barn som er hel og halvsøsken

• Ca 3600 tvillinger

• Starter i svangerskapet

• Psykisk helse hos foreldre og barn opp til 8 år.

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IToR

• By using an extended children-of-twins design, we will estimate genetic, shared

environmental, and direct environmental

modes of intergenerational transmission of risk from:

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IToR – mål 1

Alkoholmisbruk i svangerskapet

Internaliserende og eksternaliserende vansker, ADHD

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G

E E

En genetisk informativ intergenerasjonell studie på alkoholbruk og psykiske helse

• Assosiasjon

• Konfundering

• Kontrafaktisk betingelse

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MATERNAL ALCOHOL USE DURING

PREGNANCY AND OFFSPRING ADHD:

A PROSPECTIVE SIBLING CONTROL STUDY

Espen Eilertsen

Line C. Gjerde, Ted Reichborn-Kjennerud, Ragnhild E. Ørstavik, Gun Peggy Knudsen, Camilla Stoltenberg, Nikolai Czajkowski, Espen Røysamb, Kenneth S. Kendler, Eivind Ystrom

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IToR – mål 1

ADHD

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Association between maternal alcohol use during pregnancy and the two measures of ADHD symptoms

• Model 1, crude association.

• Model 2, association adjusted for measured covariates.

• Model 3, difference between maternal alcohol use during

pregnancy and before pregnancy, adjusted for measured covariates.

• Model 4, association estimated from sibling comparison, adjusted for measured covariates.

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Key messages

• This study investigated the potential causal relationship between maternal alcohol use during pregnancy and offspring ADHD.

• Controlling for confounding using observed covariates, a negative control and sibling comparison, we found an association for ADHD symptoms, but not for clinical diagnoses.

• The results are consistent with a weak, causal relationship between maternal alcohol use during pregnancy and offspring ADHD.

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Maternal alcohol consumption in pregnancy and internalizing and externalizing behavior problems in preschool children: a sibling control study

Ingunn Olea Lund

Espen Moen Eilertsen, Line C. Gjerde, Espen Røysamb, Ted Reichborn-Kjennerud &

Eivind Ystrom

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IToR – mål 1

Internaliserende og eksternaliserende vansker

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Key messages:

• The study investigated whether there could be a causal association between hazardous drinking during the 1st trimester and offspring behavior problems.

• We found associations between hazardous drinking during the 1st

trimester and child behavior problems, but all associations disappeared after sibling control.

• A causal effect of moderate to hazardous drinking during the 1st trimester and child behavior problems is therefore unlikely.

• Regardless, our study does not suggest that it is safe to drink while

pregnant, given the strong evidence that hazardous drinking contributes to other severe outcomes, such as FAS.

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IToR – mål 2

Samtidig alkoholmisbruk

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Knudsen, A. K., Ystrom, E., Skogen, J. C., & Torgersen, L. (2015). Maternal heavy alcohol use and toddler behavior problems: a fixed effects regression analysis.

European child & adolescent psychiatry, 24(10), 1269-1277.

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IToR – mål 3

ADHD

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Genetic and environmental contributions to early

development of ADHD related symptoms

Espen Eilertsen

Line Gjerde

Ted Reichborn-Kjennerud Espen Røysamb

Kenneth S. Kendler Eivind Ystrøm

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IToR – mål 4

Angst og depresjon

Under svangerskap og senere

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Gjerde et al. (2017)

Depresjon hos mor og problemer hos barnet

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Gjerde et al. (2017)

• Effekten av mors

depresjon stiger med alder.

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Angst hos mor og problemer hos barnet

Gjerde et al. EVIDENSE OF DIRECT ENVIRONMENTAL LINK BETWEEN PRESCHOOL MATERNAL ANXIETY SYMPTOMS AND OFFSPRING INTERNALIZING PROBLEMS

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Mors angst og problemer hos barnet

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Konklusjon

• Spesifikke effekter av samtidig angst hos mor, men kun på internaliserende problemer hos barnet i førskolealder.

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Maternal symptoms of anxiety and depression and child nocturnal

awakenings at 6 and 18 months

Eivind Ystrom, Mari Hysing, Leila Torgersen, Hilde Ystrom, Ted Reichborn- Kjennerud, Børge Sivertsen. Journal of Pediatric Psychology.

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• Depresjon/angst hos mor og barns søvnvansker er assosierte.

• Oppvåkninger hos barnet.

1. Mor-drevet?

2. Barne-drevet?

3. Felles risikofaktorer?

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Konklusjoner

• Ved 6 måneder var assosiasjonen fordelt på flere ulike stier (mor- drevet, barn-drevet, felles faktorer).

• Ved 18 måneder kunne assosiasjonen forklares av en mor-drevet modell

• Depresjon: 0.12 (odds ratio = 1.73)

• Angst: 0.10 (odds ratio 1.67).

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Videre planer

• Biometriske analyser

• Genetisk korrelasjon mellom lidelse hos voksen og barn.

• F.eks.

• ADHD

• Alkoholmisbruk unders

svangerskapet

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Genetikk

Molekylærgenetikk (1910-1925) Kvantitativ genetikk (1921)

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Genetikk i dag

Molekylærgenetikk Kvantitativ genetikk

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Genome wide complex trait analysis (GCTA)

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Genome wide complex

trait analysis (GCTA)

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GCTA:

Genomic and phenotypic similarity in unrelated individuals

Genomic similarity

S1 S2 S3 S4

S1 +0.1% -0.5% +0.1%

S2 -0.2% +0.5%

S3 +0.2%

S4

Phenotypic Similarity

S1 S2 S3 S4

S1 ++ -- +

S2 - ++

S3 +

S4

S1

E A

S2

A E

+0.1%

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CAPICE:

Childhood and Adolescence Psychopathology:

unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe

• MARIE SKŁODOWSKA-CURIE ACTIONS

• Innovative Training Networks (ITN)

• Call: H2020-MSCA-ITN-2016

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CAPICE

Consortium

Member Country

Dept./

Division / Laboratory

Scientist-in-Charge

Stichting VU- VUMC

NL Biological Psychology Dr CM Middeldorp, MD, PhD

King’s College London

UK Social, Genetic &

Developmental Psychiatry Centre

Prof Dr R. Plomin, PhD

Göteborgs Universitet

SE Institute of

Neuroscience and Physiology

Dr S Lundström, PhD

University of Bristol

UK School of Experimental Psychology

Prof Dr MR Munafò, PhD

Erasmus Universitair Medisch Centrum Rotterdam

NL Child and Adolescent Psychiatry

Prof Dr H Tiemeier, MD, PhD

Karolinska Institutet

SE Medical Epidemology and Biostatistics

Prof Dr P Lichtenstein, PhD

Consortium

Member Country

Dept./

Division / Laboratory

Scientist-in- Charge

CITO NL Psychometrisch

Onderzoeks- en Kenniscentrum

Dr C. Sluijter, PhD

Genalice NL Bioinformatics department Dr B Tolhuis, PhD

Norwegian Institute of Public Health

NO Genetics, Environment and Mental Health

Dr. Eivind Ystrøm, PhD

GAMIAN- Europe BE R Nica, MSc

Universiteit Twente

NL Research Methodology, Measurement and Data- Analysis

Dr S van den Berg, PhD

Universita Degli Studi Di Cagliari

IT Surgical Science Prof V Fanos, MD

Imperial College of Science Technology and Medicine

UK Epidemiology and

Biostatistics

Prof dr MR R Järvelin, PhD

Janssen-Cilag AB SE Research and development

Dr WC Drevets, MD

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CAPICE:

Childhood and Adolescence Psychopathology:

unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe

Figure 1: Structure of CAPICE: WP1-4 are the research packages focusing on the influence of risk factors on mental health symptoms. The WPs are

distinguished by the main methodology used and, therefore, the project

objectives are investigated across WPs (see objectives box). The interplay with the environment is investigated in all 4 WPs.

All results are disseminated to scientists, clinicians and the general public

coordinated by WP5. Training including research, transferable and

complementary skills is organized in WP6. WP7 is responsible for the management.

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IToR

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“ITOR2”:

INTERGENERATIONAL TRANSMISSION OF INTERNALIZING AND EXTERNALIZING

PSYCHOPATHOLOGICAL S^PECTRA: Â GÊNOME-^WIDE CÔMPLEX T^RAIT S^TUDY

• December 1 2017 to June 2021

• PI: E Ystrøm

• 1 postdoc, 1 researcher, 15% administrative support, 10% PI.

• 5% salary for 2 international co-investigators (Thalia Eley and Fruhling Rijsdijk).

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• assortative mating might explain why

• I) mental disorders are so heritable despite being associated with reduced fecundity

• II), why some mental disorders are much more heritable than others, and

• III) why there are common genetic risk factors for mental disorders

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Variables

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IToR2

Molekylærgenetikk Kvantitativ genetikk

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Behavorial Genetics Association Annual Meeting (BGA)

• Konferanse på genetikk og psykisk helse / rusmiddelforskning

• Oslo 28. juni til 1. juli.

• http://www.bga2017.no

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Minnesota Twins reared apart

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Minnesota Twins reared apart

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Minnesota Twins reared apart

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Behavorial Genetics Association Annual Meeting (BGA)

• Konferanse på genetikk og psykisk helse / rusmiddelforskning

• Oslo 28. juni til 1. juli.

• http://www.bga2017.no