Association between 2D:4D Ratio and Brain Connection Development 129testosterone has profound effects on fetal brain morphology, both in male and
female fetal brain cells exposed to various concentrations of testosterone
(unpublished data) [2, 62–66].
Maternal circulating testosterone has also been used in the past as a proxy
measure for fetal testosterone. Since testosterone is lipid soluble, it can cross
the placenta and bidirectional transfer between the mother and fetus is theo-
retically possible. Association between maternal circulating testosterone and
fetal testosterone has been observed in numerous studies [3–30,63–66] and
maternal circulating levels have been tied to gender role behavior in some
young children (reviewed in Refs [3–6]). However, some studies suggest that
maternal circulating testosterone may only affect female fetuses [42,43].
Association between 2D:4D Ratio and Brain
Connection Development
Although associations have been observed between 2D:4D, maternal circulating
testosterone [3–6,31], and ASD characteristics, variable results highlight the need
for larger studies, particularly studies that include assessment of gender effects. In
a recent analysis of 2D:4D ratio and social communication and emotional recog-
nition issues characteristic of autism, the evidence did not strongly support a link
between digit ratio and recognition of low intensity faces (reviewed in Ref. [67]).
However, low right‐hand digit ratio was associated with those in the highest per-
centage for autistic traits and individuals who had difficulty recognizing facial
expressions and correctly interpreting emotions. Lower 2D:4D ratios have also
been linked to maternal circulating testosterone in certain populations and may
be a valid proxy in certain populations, but evidence does not support an overall
link between circulating maternal testosterone during pregnancy and subsequent
social communication and recognition of emotion. However, it must be realized
that these discrepancies are most likely due to timing of exposure to testosterone
or similar acting chemicals found in fragrances and food flavors and our environ-
ment [33,34,44–60,63–66]. In Chapter 7 we describe some of the chemicals that
either act like testosterone or act on androgen receptors and activate the recep-
tors, essentially activating the signaling pathways that testosterone would do in a
natural gestation environment, except the effect would be amplified.
The authors proposed two possible explanations for the failure to replicate
previous studies that showed a link between autistic traits and 2D:4D ratios.
The first explanation revolved around potential bias due to gender influences
that could have affected the evaluation of the systemizing and empathizing
measures. The second explanation suggested the presence of a threshold effect
in which in a nonlinear relationship between fetal testosterone and ASD traits,
high levels of fetal testosterone may be required to predispose males to devel-
opment of ASD traits [67].