Identification of biobehavioral markers of neurodevelopmental disorders in twins
Willfors, Charlotte
2017-03-03
13.00
Sal Leo/Hans, KIND/CAP, plan 8, Gävlegatan 22 B, Stockholm
Inst för kvinnors och barns hälsa / Dept of Women's and Children's Health
Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are
complex neurodevelopmental disorders (NDD), heterogeneous in phenotypes and etiology.
The exact mechanisms driving the phenotypes are still largely unknown. The overall aim of
this thesis is to find new leads for ASD and ADHD etiology, focusing on environmental
factors through the examination of discordant twins. For this purpose, two ASD enriched and
well characterized twin cohorts were investigated; the Roots of Autism and ADHD Twin
Study of Sweden (RATSS) and the Californian Autism Twin Study (CATS). In study I, we
are discussing the background the aims and the rationale for the RATSS program.
In study II, the association between ASD and IQ is examined. There is a robust and negative
phenotypic correlation between IQ and ASD, categorical as well as dimensional, underpinned
by genetic and non-shared environmental (NSE) factors. The role of non-shared environment
in ASD, focusing on early medical events, is explored in Study III. There is an association
between the total load of early medical events and ASD, both categorically as well as
dimensionally defined. The association is particularly driven by behavioral dysregulation in
infants (feeding and sleeping problems, excessive crying and worriedness) as a function of
NSE factors. In study IV, we test the hypothesis of a link between ASD and pre- and
postnatal dysregulation of metals. ASD cases demonstrate higher lead levels during a period
of 20 weeks before and 30 weeks after birth, lower manganese levels 17 weeks prenatally to
30 weeks postnatally, and a reduction in zinc 10 weeks prenatally to five weeks postnatally.
In study V we study executive functioning as a behavioral marker of ADHD. There is a link
between ADHD on one hand, and foresighted planning and inhibitory control on the other
hand, mediated by NSE factors.
In summary, the findings support ASD to be continuously distributed in the population with
clinical phenotypes being the extremes of these continuums. They point to a cumulative
multifactor threshold model, including both genetic and NSE components in the etiology of
ASD. More specifically, the results support that systemic pre- and postnatal elemental
dysregulation increase ASD risk, and an association between early medical events and ASD
risk. The findings also indicate low IQ to be a behavioral marker for ASD, and poor
executive functioning to be a behavioral marker for ADHD. Both these association are
underpinned by NSE factors.