PROVINCIAL OUTREACH PROGRAM FOR FETAL ALCOHOL SPECTRUM DISORDER

1. PROVINCIAL OUTREACH PROGRAM FOR FETAL ALCOHOL SPECTRUM DISORDER Update on current research Anne George Assistant Professor, Faculty of Medicine, UBC Adjunct Professor, Health Sciences, UNBC Richmond, BC, October 29, 2008

2. Research in 2008 – a few examples • “Alcohol exposure during the first two trimesters-equivalent alters the development of corpus callosum projection neurons in the rat” Alcohol p285-93. • “Neonatal Alcohol-induced region-dependent changes in rat brain neurochemistry measured by high-resolution magnetic resonance spectropscopy” Alc Clin Exp Res p1697-1707. • “Environmental enrichment alters neurotrophin levels after fetal alcohol exposure in rats” Alc Clin Exp Res p1741-51. • “Maternal adrenocoricoptropin, cortisol, and thyroid hormone responses to all 3-trimester equivalent repeated binge alcohol exposure: ovine model” Alcohol p99-205. • Acute ethanol administration causes malformations but does not affect cranial morphometry in neonatal mice. Alcohol p21-7. • “Eyeblink Classical Conditioning in the Preweanling lamb” Behavioural Neuroscience p722-9.

3. Research activity • 5896 research articles to date, from databases covering literature in the fields of Education, Sociology, Psychology and Medical. • 469 articles for years 2007-2008

4. postnatal environment – Animal brain studies in animals • MRI • Neonatal handling • Enrichment of the environment • Training or therapy

5. postnatal environment – Animal brain studies in animals MRI • Progress in understanding the neurochemical affects to specific regions of the brain. • Overall reduced volume • Studies examined specific areas of the brain: • Cerebellum - volume and shape • Frontal cortex or hippocampus • Basal ganglia • One region of Basal ganglia is most affected (caudate nucleus). This region may be responsible for most of the functional deficits seen with FASD. • Results provide tools for human interventions

6. postnatal environment – Animal brain studies in animals • MRI • Neonatal handling • Enrichment of the environment • Training or therapy

7. postnatal environment – Animal brain studies in animals Neonatal handlingimproves learning, facilitates maturation and modifies neuroendrocrine responses to stressful stimuli in normal animals (Researchers: Weinberg, Gallo, Gabriel, Clausing, others) Animals prenatally exposed to alcohol  Behaviour: handling is effective in some, not all behaviours  Stress: positive effects of handling are not found in handling alcohol-effected neonates handling  Learning: findings inconclusive. Results show that handling did not ameliorate alcohol-exposure effects on spatial memory; handling may exacerbate performance deficits.

8. postnatal environment – Animal brain studies in animals • MRI • Neonatal handling • Enrichment of the environment • Training or therapy

9. postnatal environment – Animal brain studies in animals Enrichment of the environment Several studies by Hannigan, Parks, Wainwright, Clausing and others.  Behaviour: enriched environments mitigate prenatal alcohol effects on behaviour - improve functional outcomes but do not ameliorate effects on neurotrophin levels in brain.  Learning: improved spatial learning shown regardless of prenatal alcohol exposure. The complexity is that the mechanisms for these improvements are not seen in hippocampal spine density. Conclusion: while plasticity in the hippocampus is damaged by alcohol exposure, alternate mechanisms may take over.

10. postnatal environment – Animal brain studies in animals • MRI • Neonatal handling • Enrichment of the environment • Training or therapy

11. postnatal environment – Animal brain studies in animals Training or therapy • PAE animals took more time to be trained. With adequate training and once attainment is achieved, motor coordination and balance were improved so that there was no difference between PAE and non-exposed animals (Klintsova et al 2000). • Training also increased numbers of synapses on Purkinje cells. • Conclusion: Training on complex motor tasks with attainment of consistent learning criteria, and not exercise alone, ameliorates the motor and learning deficits and the effects in cerebellum.

12. Implications • We have learned lots. • We are on the verge of becoming much more refined in our knowledge. •  Exercise + training

13. Human research • Considerable research on • diagnosis and detection • reducing use during pregnancy • Targetted interventions – • Social skills training (O’Connor et al). • Children benefited in their knowledge of appropriate behaviour, but did not translate this to behaviour at school. • Social cognitive habituation (Kable et al). • Children improved in behaviour and math when their parents were included in the tutoring program and were taught about the problems and strategies associated with FASD. • Games as a teaching tool (Coles et al) • Safety was taught successfully to children with FASD.

14. Targetted interventions • Social skills training (O’Connor et al). • Children benefited in their knowledge of appropriate behaviour, but did not translate this to behaviour at school. • Social cognitive habituation (Kable et al). • Children improved in behavioural and math skills when their parents were included in the tutoring program and the parents were taught about the problems and strategies associated with FASD. • Games as a teaching tool (Coles et al) • Safety was taught successfully to 4-10 year old children with FASD. Children were able to generalize the steps required for fire and street safety.

15. Evidence synopsis – an example • The best predictor of adolescent or adult problems with alcohol is PAE. This factors is stronger than any other factor, including family history of alcoholism, nicotine exposure, and environmental conditions, including parental use postnatally (Baer et al, 2003, Chotro et al 2007) • Examination of period of exposure, • dose and administration, • genetics, • gender, • age of testing.

16. Question • What is the mechanism for this? • Neurochemical changes • Alterations in response to stress • Prenatal chemosensory learning.

17. Thank you Anne George Department of Pediatrics, Faculty of Medicine, UBC Address: c/o UNBC, Prince George ageorge@cw.bc.ca 250-960-5157