Tst gifted 08 - Templetonfellows.org

TESTOSTERONE
AND
COGNITION
the contribution to the neurobiology
of giftedness
DANIELA OSTATNIKOVA
COMENIUS UNIVERSITY FACULTY OF MEDICINE
BRATISLAVA
SLOVAKIA

WHERE IS THE SITE OF
INTELLIGENCE

Alternative PROgram for Gifted
EducatioN in Slovakia, APROGEN
The net of 27 primary schools with APROGEN classes
• 600 students in Bratislava – School founded n 1998
• 3000 pupils in Slovakia involved in this programme
The School for Intellectually Gifted in Bratislava, Slovakia
is one possible alternative for children with high academic
potential

ALBERT EINSTEIN – frontal and temporal lobes studied
In the left hemisphere, in
area 39 there were more
glial cells for every neuron in
his brain.
Higher density of supportive
cells per neuron in certain
area of the brain might
indicate an increased
"metabolic need" – neurons
need and use more energy.

FRONTAL LOBES
Grey matter amount in frontal brain regions is strongly
inherited and predicts individual's IQ scores
(Paul Thompson, Nature Neuroscience, 2001)
MRI of 20
identical twins
and 20 same
sex fraternal
twins

...“Single „intelligence center“ such as the frontal lobe, is
unlikely...“ dr. Richard Heier, 2004
His study was the first to demonstrate that
1) gray matter in specific regions in
the brain is more related to IQ than
overall size
2) Only about 6% of all gray
matter in the brain appears to be
related to IQ
3) The distribution of gray matter
in humans is highly heritable.
Researchers used voxel-based* morphometry
in 47 normal adults to determine gray matter
Volume throughout the brain which they
correlated to IQ scores
*Short for volume pixel, the smallest distinguishable box-shaped
part of a three-dimensional image

WHAT EXACTLY MAKES A PERSON
BRILLANT

NATURE as well as NURTURE
(formerly seen as incompatible perspectives)
GENES & ENVIRONMENT
INTERACTIONIST PERSPECTIVE
(interrelations between genetics & environment)
HEREDITY DETERMINES ONE´S POTENTIAL
BUT ENVIRONMENT DETERMINES HOW FAR ONE WILL REACH THAT
POTENTIAL DURING HER OR HIS LIFETIME

HORMONES ARE MESSENGERS OF
GENES
PROVIDING SPECIFIC
ENVIRONMENTAL EFFECT ON BRAIN

EFFECTS OF SEX STEROIDS ON
NEURAL STRUCTURES
SUGGESTIVE DATA HAVE ACCUMULATED
LINKING TESTOSTERONE AND ESTRADIOL
TO COGNITION IN HUMANS
SOMATIC CHARACTERISTICS
TESTOSTERONE
5-α-REDUCTASE
DIHYDROTESTOSTERONE
AROMATASE
ESTRADIOL
COGNITION
NEUROPROTECTIVE EFFECT
PREVENTION OF CELL DEATH
SYNAPTOGENESIS
DENDRITIC GROWTH

Sexual dimorphisms
in the rat brain.
HYPOTHALAMUS
ORGANIZATIONAL EFFECT
The sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in male rats (a) than
in females (b) because the testes secrete testosterone during the sensitive period. After that
time, testosterone has little effect on SDN-POA volume.
Sexual dimorphisms
in the rat brain.
AMYGDALA
ACTIVATIONAL EFFECT
In contrast, the volume of the rat posterodorsal medial amygdala (MePD), which is about 1.5
times larger in males (c) than in females (d), retains its responsiveness to testosterone
throughout life. All scale bars = 250 µm.

TESTOSTERONE LEVELS DURING ONTOGENESIS IN BOYS
Plasma testosterone (nmol/L)
30
15
foetus childhood puberty adulthood senescence
ORGANIZATION
ACTIVATION
1. 2. 3. 1 10 17 40 60 80
trimester
age in years

ORGANIZATIONAL EFFECT OF TESTOSTERONE
ON HUMAN INTELLIGENCE
+
RH
‣ GIFTEDNESS
mathematical
musical
spatial
↑ TST
‣ ANOMALOUS
DOMINANCE
handedness
speech
centres
_
LH
‣IMMUNE DISORDERS
(Geschwind, Behan, Galaburda; 1985, 1987)

Testosterone in nmol/L
0,050
0,045
0,040
0,035
0,030
0,025
0,020
0,015
0,010
0,005
gifted
control
0,000
6 years 7 years 8 years 9 years
SALIVARY TESTOSTERONE LEVELS IN CHILDREN
THROUGHOUT PREADOLESCENCE
(Ostatníková et al., High Ability Studies, 2000; BMC Pediatrics, 2002)

SALIVARY TESTOSTERONE LEVELS IN PREPUBERTAL
CHILDREN GROUPED BY SEX AND IQ
Ostatníková et al., Neuropsychologia, 2007

• Significant differences in salivary
testosterone levels were found in boys
grouped by IQ, no difference was
observed in girls
• In general it was no difference in
academic intelligence between
preadolescent boys and girls
• Boys were overrepresented in minority
population groups related to IQ (gifted
and mentally disabled)
CONCLUSIONS

1. High levels of testosterone prenatally
(Geschwind & Galaburda, 1985) cause lower
postnatal setup of H-P-G axis by negative
feedback, which could stay as a predictor of
later puberty onset in gifted boys
2. Higher sensitivity of tissues to testosterone
might also explain the lower levels in boys
HYPOTHESES EXPLAINING LOWER
TESTOSTERONE IN GIFTED BOYS

LOOKING AT THE
MATURATION ONSET

Salivary testosterone during puberty
in boys
gifted
control
0,7
0,6
testosterone [nmol/l]
0,5
0,4
0,3
0,2
0,1
0
8 9 10 11 12 13 14 15 16 17
age [years]
TESTOSTERONE FLUCTUATIONS IN BOYS
DURING CHILDHOOD AND PUBERTY

Age at menarche
13.5
13.0
age [years]
12.5
12.0
11.5
11.0
control
gifted
AGE OF MENARCHE IN GIRLS

• Prepubertal levels were not
associated with puberty onset in
boys in our study
• Speculations about early
maturation of controls or late
maturation of gifted were not
confirmed
CONCLUSIONS

LOOKING AT THE
GENES
RELATED TO TESTOSTERONE
METABOLISM

PLASMA TESTOSTERONE (ITS FREE FRACTION)
ACTS ON TARGET TISSUES AND
MEDIATES ITS ANDROGENIC EFFECT
TESTOSTERONE
VIA
5-ALPHA
REDUCTASE
AROMATASE
ANDROGEN
RECEPTOR
DIHYDROTESTOSTERONE
ESTRADIOL
ESTROGEN
RECEPTOR
GENOMIC EFFECT OF SEX HORMONES

ANDROGEN RECEPTOR- looking for its sensitivity to androgens
• Intracellular transcription factor
• Gene for androgen receptor is located on chromosome X
• Polymorphism in the 1st exon of AR gene – polyglutamine
(CAG)n repetitive segment
• Average number of repeats 21 ± 2 (normal range 9 – 37)
Decreased number of CAG repeats
• – higher sensitivity of AR
• – higher androgenic effect
ANDROGEN RECEPTOR –
MEDIATOR OF TESTOSTERONE EFFECT

• PROBANDS
• 139 intellectually gifted (95 boys) age 12-18
(IQ>130)
Special school for intellectually gifted in Bratislava,
Slovakia
• 122 controls (67 boys) age 12-18 (70

SNP/STR Gene Description Locus Allels
rs415620 CYP21A2 cytochrome P450 21; steroid 21-hydroxylase 6p21.3 A/G
rs3822430 SRD5A1 3-oxo-5-alpha-steroid 4-dehydrogenase 1 5p15.31 C/T
rs632148 SRD5A2 3-oxo-5-alpha-steroid 4-dehydrogenase 2 2p23.1 C/G
rs700518 CYP19A1 cytochrome P450 19A1; aromatase 15q21 A/G
rs2077647 ESR1 estrogen receptor alpha 6q24-q27 A/G
rs928554 ESR2 estrogen receptor beta 14q21-q22 A/G
rs1799941 SHBG sex hormone binding globulin precursor 17pter-p12 A/G
rs9282858 SRD5A2 5 alpha reductase 2p23.1 C/T
C1558T CYP19A1 cytochrome P450 19; aromatase 15q21 C/T
CAG STR AR androgen receptor Xq11-12 (CAG)n
ANALYSED GENE POLYMORPHISMS

ANDROGEN RECEPTOR GENE POLYMORPHISM IN
GIFTED AND CONTROL BOYS
THE LOWER THE CAG
TRIPLET REPEATS IN AR
GENE THE HIGHER
ITS SENSITIVITY AND
ANDROGENIC EFFECT IN
TARGET TISSUES INCLUDING
BRAIN
= lower testosterone level is
needed for its effect in target
cells
= explanation for lower
testosterone levels in gifted
boys

• This is the first study analyzing
polymorphisms of genes related to
testosterone metabolism in relation to
academic intelligence
• Gene variants of ESR2 (estrogen receptor)
and SHBG (sex hormone binding globulin)
showed different frequencies in gifted boys
compared to control boys, the phenotypical
consequences are unknown
CONCLUSIONS

• Intellectually gifted boys had lower
(CAG)n repeats in AR gene, known to be
associated with increased androgen
signaling
• Increased androgen signaling might
account for lower testosterone levels in
prepubertal gifted boys
CONCLUSIONS

• Neurobiological studies need many
subjects to be able to prove the
difference
• Neurobiological studies need the
interdisciplinar cooperation
INVITATION TO PARTICIPATE

THANK YOU FOR YOUR ATTENTION
AND TO ALL MY CO-WORKERS, CHILDREN AND THEIR
PARENTS FOR COOPERATION
THE PROJECT WAS SUPPORTED BY Scientific grant agencies of Ministry of Education and Ministry
of Health of Slovak Republic No.1/3420/06 , 4/0038/07, 2006/22-UK-01