Van der Meere, Börger, & Wiersema (submitted)
Mean
frequencyfrequentie
facial movements
Gemiddelde
lipspart
30
20
Aantal
10
jjjjj
jjjjj
jj
group
groepscode
Controle
0
ADHD
1
2
Periode
Time
on task
3
4
5
6
Brain/HR/Facial movements
Venous Volume
Lateral hypothalamic
area
RVLM
Anterior
cingulate cortex
Nts
IML
Systemic Resistance
Sympathetic
Heart
&
Circulation
Maximum Elastance
(Control Center)
NA
Heart Rate
(Parasympathetic)
PA
Baroreceptors
conclusion
 ADHD
associated with poor state
regulation (underactivation) : in common
parlance “poor motivation.
 More
research needed on factors that
regulate energy metabolism in ADHD
Genetics and state regulation
100%
90%
80%
Other
70%
60%
child-specific
environment
shared environment
50%
40%
30%
20%
additive genes
10%
0%
S
F
Go/No-Go Task
I
BL
F-I
Fast Task
S+BL
Combined
Minor disabilities
 Lower
IQ level but in the normal range
 Mild motor impairment
 Poor memory language skills
 30 to 50 of the children with VLBW follow
special education
Longitudinal study of the
effects of maternal anxiety and
stress during pregnancy :
Neuropsychological examination
of attention and inhibition
functions in adolescents
Mechanisms


On the basis of animal research in rats and non-human
primates, and of epidemiological research in humans,
suggested potential mechanisms are:
Placental transfer of maternal stress-related hormones:
 does maternal cortisol influence the development of
the fetal brain?(fetal programming hypothesis)
 are the fetal extrahypothalamic CRH, glucocorticoid
system (limbic system and HPA-axis)and brainstem
particularly sensitive to these early influences?)
Anxiety of the mother.

Measure:
 -state anxiety (situational momentory anxiety),
 -trait anxiety (personality)

result: the more anxiety the mother shows, the
more movements made by the unborn child.
Relation featal behavior neonatal behavior
 Correlations
were between .34 to .67
 measured five days after delivery.
Results of follow-up,wave 1
(0 - 7 months after birth)
Maternal anxiety during pregnancy :

explains 10-25% of the variance in:
 fetal and neonatal behavioural state organization
(time ‘awake’) and state-dependent activity
 in irritability, excessive crying, irregularity in
biological functions, difficult temperament during
the first seven months after birth (temperament was
measured with ITQ (Carey et al.) IC Q (Bates et al.)

has no effect on neonatal neurological state, infant
feeding behaviour, mental and motor development
(Bayley scales) (Van den Bergh,1990, 1992; Van den Bergh et al., 1989)
Results of follow-up, wave 2
(8-9 years)

After controlling for covariates (birth weigth, cigarette
smoking of mother during pregnancy, postnatal maternal
anxiety were entered as first step in hierarchical MR)
prenatal maternal anxiety measures explained:


In boys: 11 to 42 % of the variance in self-regulation measures
(effortful control, attention, inhibitory control, hyperactivity)
In girls 11 to 19 % of the variance in self-regulation measures
(extraversion, impulsivity, activity, acting-out)
(measured with CBQ (Children’s Behavior Questionnaire; Rothbart), CARTS
Conners ’ Abbreviated Teacher Rating Scale), GBO (Groninger Behavior
Observation Scale; Kalverboer)).

Results were found with questionnaires completed by
mother, (blind) teacher and (blind) observer
(Van den Bergh, 2001, summitted; Van den Bergh et al., 1999)
Prediction of self-regulation at 8/9 years from maternal
anxiety during pregnancy and covariates (in %). Boys
Observer:
GBO
Teacher:
CATRS
Variance explained by covariates during and after pregnancy
Variance explained by measures of anxiety during pregnancy
Act
vit y
Atte
nt io
n
acti
vity
Act
ingOut
acti
vity
Act
ingOut
Mother:
CATRS
Hyp
er
Inh
ib
Effo
rt fu
l
c on
t rol
itor
Atte
y co
nt io
nt ro
nal
l
Ext
f ocu
rave
ssin
rs io
g
n/s u
rgen
cy
Im p
ulsi
vity
Act
ivity
leve
Mot
l
or a
ctiv
at io
n
Mother:
CBQ
Hyp
er
80
70
60
50
40
30
20
10
0
Prediction of self-regulation at 8/9 years from maternal
anxiety during pregnancy and covariates (in %). Girls
80
70
60
50
40
30
20
10
0
Mother:
CATRS
Variance explained by covariates during and after pregnancy
Variance explained by measures of anxiety during pregnancy
Child:
STAIC
Stat
e
ty
Observer:
GBO
Act
vi
t
g-O
u
vity
Act
in
ract
i
Hyp
e
t
g-O
u
vity
Act
in
ract
i
Hyp
e
ibito
Teacher:
CATRS
Inh
Effo
r
tful
con
trol
r
y
Atte
con
trol
ntio
n
al fo
Ext
cuss
rave
ing
rsio
n/su
rgen
cy
Imp
ulsi
vity
Act
ivity
leve
Mo
l
tor
acti
vati
on
Mother:
CBQ
Prediction of self-regulation at 14/15 years from maternal
anxiety during pregnancy and covariates (in %). Boys
80
70
60
50
40
Mother:
EATQ- R
Teacher:
CATRS
30
Child:
STAIC
20
10
Variance explained by covariates during and after pregnancy
Variance explained by measures of anxiety during pregnancy
xiet
y
e An
Stat
Hyp
er ac
tivit
y
Act
ing
O ut
Act
ivat
ion
Con
trol
Inh
ibito
ry C
ontr
ol
Atte
nt io
n
Sur
gen
cy
Shy
ness
Fru
stra
t ion
Affi
liati
on
Agg
resi
on
0
Prediction of self-regulation at 14/15
years from maternal anxiety during pregnancy and
covariates (in %). Girls
80
70
60
Mother:
EATQ-R
50
Teacher:
CATRS
40
30
20
10
Variance explained by covariates during and after pregnancy
Variance explained by measures of anxiety during pregnancy
Fea
r
ut
gO
Act
in
vity
ract
i
Hyp
e
em
ood
Dep
r
essi
v
n
essi
o
Agg
r
ess
Shy
n
tion
Atte
n
ry C
ontr
ol
ibito
Inh
Act
iv
atio
n
Con
trol
0
Discussion

After controlling for confounding variables,
there is still a significant effect of maternal
prenatal and postnatal anxiety on measures
of temperament, behaviour and emotion in 14
and 15 year olds.
 The gender effect found in waves 1 and 2 of
the longitudinal study was replicated in these
results.

For boys prenatal maternal anxiety measures
seem to influence temperamental dispostions and
postnatal behaviour which imply self regulatory
mechanisms at the age of 14 and 15.
Conclusion
 Prenatal
environmental factors - such
as maternal anxiety - have an
influence on the phenotypic variation
in neurobehavioral functioning
 Study
of “early programming” of the brain
has the potential of gaining more insight
in normal and abnormal
neurodevelopmental processes
Sustained attention test
800
700
Girls
Boys
600
500
Period 1
Period 6
Standard Deviation of rt, CPT
350
300
Girls
Boys
250
200
150
Period 1
Period 6
Boys: Anxiety groups, SD,
CPT
450
400
350
low Anx
medium Anx
high Anx
300
250
200
150
Period 1
Period 6
Girls: Anxiety groups, SD,
CPT
450
400
350
low Anx
medium Anx
high Anx
300
250
200
150
100
Period 1
Period 6
Conclusions
 Boys
have in general more problems with
state regulation and sustained attention
than girls (note: the ratio ADHD boys and
girls is 6 :1).
Genetics and state regulation
100%
90%
80%
Other
70%
60%
child-specific
environment
shared environment
50%
40%
30%
20%
additive genes
10%
0%
S
F
Go/No-Go Task
I
BL
F-I
Fast Task
S+BL
Combined
Treatment
Methylphenidate alone is more effective than behavioral intervention
The combination is even better
Side effects?
Long run?