On the Spectrum

General discussion
in etiologies and resulting growth abnormalities could be greater at the severe end of the
autistic trait spectrum, and may, as a result, not form a continuous extension of the association
observed in relation to milder traits. Of note, both microcephaly and macrocephaly have
been implicated in ASD (Fombonne, Roge, Claverie, Courty and Fremolle 1999). Perhaps,
only a subset of etiologic pathways to clinical ASD involve macroscopic prenatal brain
growth changes. Likewise, while many children with ASD do not show differences in head
circumference at birth, it is thought that only a subset of children may show abnormally large
head size (Green, Loesch and Dissanayake 2015). It is possible that such pathways are less
involved in autistic traits in the general population.
Postnatal brain characteristics: structure and function
Postnatal development of the cortex is a dynamic process of several phases. There are
different aspects of the cortex, each originating from different stages in neurodevelopment
and regulated by at least partly independent genetic mechanisms (Shaw, Kabani, Lerch,
Eckstrand, Lenroot et al. 2008; Panizzon, Fennema-Notestine, Eyler, Jernigan, Prom-Wormley
et al. 2009; Raznahan, Shaw, Lalonde, Stockman, Wallace et al. 2011). Cortical thickness is
defined as the area between the white matter surface and the gray matter surface and is
likely related to the number of neurons and neuronal density (Herculano-Houzel, Watson and
Paxinos 2013). Surface-based methods have enabled us to study this measure quite precisely
at a large number of locations in the cortex (Fischl and Dale 2000). Development of cortical
thickness has traditionally been conceptualized as an inverted-U shaped process, with initial
expansive growth in early childhood, up to a local maximum, after which the cortex becomes
thinner through a functionally selective process of “pruning” (Giedd, Blumenthal, Jeffries,
Castellanos, Liu et al. 1999). However, more recently, it has been suggested that cortical
thickness generally follows a simple linear decline in most cortical areas by age 5, and all
areas by age 8 (Ducharme, Albaugh, Nguyen, Hudziak, Mateos-Perez et al. 2016). Altered
development of the cortex is implied in a variety of neuropsychiatric disorders, including
ADHD and ASD (Wallace, Dankner, Kenworthy, Giedd and Martin 2010; Shaw, Malek, Watson,
Sharp, Evans et al. 2012). In chapter 2, we found that boys with more autistic traits had thicker
cortex in the pericalcarine area, indicating gender specificity in morphological differences in
ASD, consistent with observations in adults (Lai, Lombardo, Suckling, Ruigrok, Chakrabarti et
al. 2013). Speculatively, thicker cortex in this age range may point to a developmental delay.
One other aspect of cortical morphology is gyrification, or the folding of the brain into a
complex pattern of sulci and gyri. This is a poorly understood phenomenon that is thought
to accommodate efficient neural processing in the brain (Van Essen 1997). The majority
of gyrification takes place in the third trimester of pregnancy, at a time when the brain
undergoes prolific growth. However, the many primary sulci are formed before that, between
20 and 28 weeks of gestational age (Habas, Scott, Roosta, Rajagopalan, Kim et al. 2012) and
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