Van der Meere, BVan der Meere, Böörger, & Wiersema (submitted)rger, & Wiersema (submitted)

Gemiddelde frequentie lipspart

Periode

654321

Aa

nta

l

30

20

10

0

groepscode

Controle

ADHD

Mean frequency facial movements

jjjjjjjjjjjj

group

Time on task

Brain/HR/Facial movementsBrain/HR/Facial movements

Lateral hypothalamic area

Anterior cingulate cortex

Nts(Control Center)

RVLM IML

NA(Parasympathetic)

Venous Volume

Systemic Resistance

Maximum Elastance

Heart Rate

Heart&

Circulation

Baroreceptors

Sympathetic

PA

conclusionconclusion

ADHD associated with poor state ADHD associated with poor state regulation (underactivation) : in common regulation (underactivation) : in common parlance “poor motivation.parlance “poor motivation.

More research needed on factors that More research needed on factors that regulate energy metabolism in ADHD regulate energy metabolism in ADHD

Genetics and state regulationGenetics and state regulation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

S F I BL F-I S+BL

Other

child-specificenvironment

shared environment

additive genes

Go/No-Go Task Fast Task Combined

Minor disabilitiesMinor disabilities

Lower IQ level but in the normal rangeLower IQ level but in the normal range Mild motor impairmentMild motor impairment Poor memory language skillsPoor memory language skills 30 to 50 of the children with VLBW follow 30 to 50 of the children with VLBW follow

special educationspecial education

Longitudinal study of Longitudinal study of the effects of maternal the effects of maternal

anxiety and stress during anxiety and stress during pregnancy : pregnancy :

Neuropsychological Neuropsychological examination of attention examination of attention and inhibition functions in and inhibition functions in

adolescentsadolescents

Mechanisms Mechanisms

On the basis of animal research in rats and non-human On the basis of animal research in rats and non-human primates, and of epidemiological research in humans, primates, and of epidemiological research in humans, suggested potential mechanisms aresuggested potential mechanisms are::

Placental transfer of maternal stress-related hormones: Placental transfer of maternal stress-related hormones: does maternal cortisol influence the development of does maternal cortisol influence the development of

the fetal brain?(fetal programming hypothesis) the fetal brain?(fetal programming hypothesis) are the fetal extrahypothalamic CRH, glucocorticoid are the fetal extrahypothalamic CRH, glucocorticoid

system (limbic system and HPA-axis)and brainstem system (limbic system and HPA-axis)and brainstem particularly sensitive to these early influences?particularly sensitive to these early influences?) )

Anxiety of the mother.Anxiety of the mother.

Measure: Measure: -state anxiety (situational momentory anxiety), -state anxiety (situational momentory anxiety), -trait anxiety (personality)-trait anxiety (personality)

result: the more anxiety the mother shows, the result: the more anxiety the mother shows, the more movements made by the unborn child.more movements made by the unborn child.

Relation featal behavior - Relation featal behavior - neonatal behaviorneonatal behavior

Correlations were between .34 to .67Correlations were between .34 to .67 measured five days after delivery.measured five days after delivery.

Results of follow-up,wave 1Results of follow-up,wave 1 (0 - 7 months after birth) (0 - 7 months after birth)

Maternal anxiety during pregnancyMaternal anxiety during pregnancy : : explains 10-25% of the variance in:explains 10-25% of the variance in:

fetal and neonatal behavioural state organization fetal and neonatal behavioural state organization (time ‘awake’) and state-dependent activity (time ‘awake’) and state-dependent activity

in irritability, excessive crying, irregularity in in irritability, excessive crying, irregularity in biological functions, difficult temperament during biological functions, difficult temperament during the first seven months after birth (the first seven months after birth (temperament was temperament was measured with ITQ (Carey et al.) IC Q (Bates et al.) measured with ITQ (Carey et al.) IC Q (Bates et al.)

has no effect on neonatal neurological state, infant has no effect on neonatal neurological state, infant feeding behaviour, mental and motor development feeding behaviour, mental and motor development (Bayley scales) (Bayley scales) (Van den Bergh,1990, 1992; Van den Bergh et al., 1989) (Van den Bergh,1990, 1992; Van den Bergh et al., 1989)

Results of follow-up, wave 2Results of follow-up, wave 2 (8-9 years)(8-9 years)

After controlling for covariates (birth weigth, cigarette After controlling for covariates (birth weigth, cigarette smoking of mother during pregnancy, postnatal maternal smoking of mother during pregnancy, postnatal maternal anxiety were entered as first step in hierarchical MR) anxiety were entered as first step in hierarchical MR) prenatal maternal anxiety measures explainedprenatal maternal anxiety measures explained: :

In boys: 11 to 42 % of the variance in self-regulation measures In boys: 11 to 42 % of the variance in self-regulation measures (effortful control, attention, inhibitory control, hyperactivity) (effortful control, attention, inhibitory control, hyperactivity)

In girls 11 to 19 % of the variance in self-regulation measures In girls 11 to 19 % of the variance in self-regulation measures

(extraversion, impulsivity, activity, acting-out)(extraversion, impulsivity, activity, acting-out) (measured with CBQ (Children’s Behavior Questionnaire; Rothbart), CARTS (measured with CBQ (Children’s Behavior Questionnaire; Rothbart), CARTS

Conners ’ Abbreviated Teacher Rating Scale), GBO (Groninger Behavior Conners ’ Abbreviated Teacher Rating Scale), GBO (Groninger Behavior Observation Scale; Kalverboer)).Observation Scale; Kalverboer)).

Results were found with questionnaires completed by Results were found with questionnaires completed by mother, (blind) teacher and (blind) observer mother, (blind) teacher and (blind) observer

(Van den Bergh, 2001, summitted; Van den Bergh et al., 1999)(Van den Bergh, 2001, summitted; Van den Bergh et al., 1999)

Prediction of self-regulation at 8/9 years from maternal Prediction of self-regulation at 8/9 years from maternal anxiety during pregnancy and covariates (in %). Boysanxiety during pregnancy and covariates (in %). Boys

01020304050607080

Variance explained by covariates during and after pregnancy

Variance explained by measures of anxiety during pregnancy

Mother: CBQ Mother:

CATRS

Teacher: CATRS

Observer: GBO

Prediction of self-regulation at 8/9 years from maternal Prediction of self-regulation at 8/9 years from maternal anxiety during pregnancy and covariates (in %). Girlsanxiety during pregnancy and covariates (in %). Girls

01020304050607080

Eff

ortf

ul c

ontr

olIn

hibi

tory

con

trol

Att

entio

nal f

ocus

sing

Ext

rave

rsio

n/su

rgen

cyIm

puls

ivit

yA

ctiv

ity le

vel

Mot

or a

ctiv

atio

n

Hyp

erac

tivi

tyA

ctin

g-O

ut

Hyp

erac

tivi

tyA

ctin

g-O

ut

Act

vity

Stat

e

Variance explained by covariates during and after pregnancy

Variance explained by measures of anxiety during pregnancy

Mother: CBQ

Mother: CATRS

Teacher: CATRS Observer:

GBO

Child:STAIC

Prediction of self-regulation at 14/15 years from maternal Prediction of self-regulation at 14/15 years from maternal anxiety during pregnancy and covariates (in %). Boysanxiety during pregnancy and covariates (in %). Boys

0

10

20

30

40

50

60

70

80

Variance explained by covariates during and after pregnancy

Variance explained by measures of anxiety during pregnancy

Teacher:

CATRSChild:

STAIC

Mother:

EATQ- R

Prediction of self-regulation at 14/15Prediction of self-regulation at 14/15 years from maternal anxiety during pregnancy and years from maternal anxiety during pregnancy and

covariates (in %). Girlscovariates (in %). Girls

0

10

20

30

40

50

60

70

80A

ctiv

atio

n C

ontr

ol

Inhi

bito

ry C

ontr

ol

Att

entio

n

Shyn

ess

Agg

ress

ion

Dep

ress

ive

moo

d

Hyp

erac

tivi

ty

Act

ing

Out

Fear

Variance explained by covariates during and after pregnancy

Variance explained by measures of anxiety during pregnancy

Mother:

EATQ-RTeacher: CATRS

Discussion Discussion

After controlling for confounding variables, After controlling for confounding variables, there is still a significant effect of maternal there is still a significant effect of maternal prenatal and postnatal anxiety on measures prenatal and postnatal anxiety on measures of temperament, behaviour and emotion in 14 of temperament, behaviour and emotion in 14 and 15 year olds. and 15 year olds.

The gender effect found in waves 1 and 2 of The gender effect found in waves 1 and 2 of the longitudinal study was replicated in these the longitudinal study was replicated in these results. results. For boys prenatal maternal anxiety measures For boys prenatal maternal anxiety measures

seem to influence temperamental dispostions and seem to influence temperamental dispostions and postnatal behaviour which imply self regulatory postnatal behaviour which imply self regulatory mechanisms at the age of 14 and 15.mechanisms at the age of 14 and 15.

ConclusionConclusion

Prenatal environmental factors - such Prenatal environmental factors - such as maternal anxiety - have an as maternal anxiety - have an influence on the phenotypic variation influence on the phenotypic variation in neurobehavioral functioning in neurobehavioral functioning

Study of “early programming” of the brain Study of “early programming” of the brain has the potential of gaining more insight has the potential of gaining more insight in normal and abnormal in normal and abnormal neurodevelopmental processesneurodevelopmental processes

500

600

700

800

Period 1 Period 6

GirlsBoys

Sustained attention test

150

200

250

300

350

Period 1 Period 6

GirlsBoys

Standard Deviation of rt, CPT

BoysBoys: Anxiety groups, SD,: Anxiety groups, SD, CPT CPT

150

200

250

300

350

400

450

Period 1 Period 6

low Anxmedium Anxhigh Anx

GirlsGirls: Anxiety groups, SD,: Anxiety groups, SD, CPT CPT

100

150

200

250

300

350

400

450

Period 1 Period 6

low Anxmedium Anxhigh Anx

ConclusionsConclusions

Boys have in general more problems with Boys have in general more problems with state regulation and sustained attention state regulation and sustained attention than girls (note: the ratio ADHD boys and than girls (note: the ratio ADHD boys and girls is 6 :1). girls is 6 :1).

Genetics and state regulationGenetics and state regulation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

S F I BL F-I S+BL

Other

child-specificenvironment

shared environment

additive genes

Go/No-Go Task Fast Task Combined

TreatmentTreatment

Methylphenidate alone is more effective than behavioral interventionThe combination is even betterSide effects?Long run?