Cognitive Genetics

Cognitive Genetics
developmental issues and an
example from PKU
Angela Brant
Scerif & Karmiloff-Smith (2005)
• 1st decade of 21st Century- “the dawn of cognitive
genetics” (Pinker, 2001).
• Can the function of specific genes be linked to
specific cognitive-level processes?
• Various methods used to examine this issue….
• Scerif & Karmiloff-Smith point out that evidence
of expression of gene A, accompanied by deficits
in cognitive function B does not necessarily mean
that A directly has a role in implementing B.
Developmental Issues
• Ignoring developmental complexities in
cognitive processes carries some potentially
erroneous assumptions
• This article reviews evidence of this in
monogenic disorders
1.Can earlier cognitive outcome be
inferred from the adult phenotype?
• Williams syndrome (WS)- adults show relative strengths
in language and face processing and weaknesses in visuospatial cognition and numerical processing
• However, infants show a different profile, with grossly
delayed vocabulary comprehension, and numerical
abilities in line with their chronological age.
• Not necessarily the case (e.g. fragile X shows consistent
difficulties at all stages)
• There may also be atypical interactions and
compensations across processes over developmental
time (WS again).
2.Single genes but uneven cognitive
• E.g. fragile X- neural changes caused by the silencing of one
protein are more relevant to the neurocomputational
requirements of some functions compared to others
• FMRP- altered dendritic spine morphology across neocortical
areas. However, dendritic spines increase in density as you
move forward in the cortex in human and non-human
• Thus, a generalized change can cause apparently localized
deficits. Mechanistic accounts of why particular deficits occur
are important to understand these patterns.
• Selective deficits are not impossible, but need to be tested
All these considerations become
more complicated when
polygenetic, complex traits are
Diamond (2002)
• Outlines various deficits found in the brains of
even supposedly well-controlled PKU
• Gives an interesting example of how the
global silencing of a single protein can cause
apparently selective and unrelated deficits.
• Also shows an example of a deficit that is
(perhaps) unrelated to abilities during
development and one that is firmly caused by
childhood phenotype.
The dopamine system and PKU
Dopamine neurons projecting from VTA to DLPFC are acutely sensitive to changes in
the supply of tyrosine as they have a higher firing rate and higher rate of dopamine
Reductions in tyrosine supply to small to have an effect on other dopamine systems
have been shown to profoundly reduce dopamine levels in prefrontal cortex.
PKU and executive functioning
• Strong effect of tyrosine availability on the DLPFC
• 1980s- problems in holding information in mind,
problem solving and ‘executive functions’ in
children with PKU on a low Phe diet (e.g.
Pennington et al, 1985)
• Children with PKU have an average IQ in the 80s
and 90s- lower than their peers and reminiscent
of the deficits seen after damage to the
prefrontal cortx
Developmental delay or lasting deficit?
All children improved over time
But…..between group differences reappeared when battery for next age
group was implemented. Deficit showed no evidence of subsiding within
age range studied.
Data do not exist to answer this question, but extended cognitive delays
likely to have profound effects even if the cognitive deficit is resolved.
Dopamine in the visual system
Witkovsky, 2004
Structural effect on contrast sensitivity
Contrast sensitivity not related to current Phe levels
Contrast sensitivity usually improves with age but the reverse is seen in PKU
Earlier-born PKU siblings perform worse than their same-age siblings
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