1. Van der Meere, Börger, & Wiersema (submitted) Mean frequency facial movements jjjjj jjjjj jj group Time on task

2. Brain/HR/Facial movements Lateral hypothalamic area Anterior cingulate cortex Nts (Control Center) RVLMIML NA (Parasympathetic) Venous Volume Systemic Resistance Maximum Elastance Heart Rate Heart & Circulation Baroreceptors Sympathetic PA

3. conclusion  ADHD associated with poor state regulation (underactivation) : in common parlance “poor motivation.  More research needed on factors that regulate energy metabolism in ADHD

4. Genetics and state regulation Go/No-Go TaskFast TaskCombined

5. 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

6. Longitudinal study of the effects of maternal anxiety and stress during pregnancy : Longitudinal study of the effects of maternal anxiety and stress during pregnancy : Neuropsychological examination of attention and inhibition functions in adolescents

7. 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) 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? ) are the fetal extrahypothalamic CRH, glucocorticoid system (limbic system and HPA-axis)and brainstem particularly sensitive to these early influences? )

8. 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.

9. Relation featal behavior - neonatal behavior  Correlations were between.34 to.67  measured five days after delivery.

10. 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 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.) 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)

11. 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 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) 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)

12. Prediction of self-regulation at 8/9 years from maternal anxiety during pregnancy and covariates (in %). Boys Mother: CBQ Mother: CATRS Teacher: CATRS Observer: GBO

13. Prediction of self-regulation at 8/9 years from maternal anxiety during pregnancy and covariates (in %). Girls Mother: CBQ Mother: CATRS Teacher: CATRS Observer: GBO Child: STAIC

14. Prediction of self-regulation at 14/15 years from maternal anxiety during pregnancy and covariates (in %). Boys Teacher: CATRS Child: STAIC Mother: EATQ- R

15. Prediction of self-regulation at 14/15 years from maternal anxiety during pregnancy and covariates (in %). Girls Mother: EATQ-R Teacher: CATRS

16. 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. 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.

17. 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

18. Sustained attention test

19. Standard Deviation of rt, CPT

20. Boys: Anxiety groups, SD, CPT Boys: Anxiety groups, SD, CPT

21. Girls: Anxiety groups, SD, CPT Girls: Anxiety groups, SD, CPT

22. 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).

23. Genetics and state regulation Go/No-Go TaskFast TaskCombined

24. Treatment Methylphenidate alone is more effective than behavioral intervention The combination is even better Side effects? Long run?