FASD -SEEING THE OTHER PERSPECTIVE

1. FETAL ALCOHOL SPECTRUM DISORDER SYMPOSIUMSEEING THE OTHER PERSPECTIVEDA DWA DA DEHS NYE>SSEPTEMBER 9, 2014 Barry Stanley. www.barrystanleyfasd.com. Docstoc bstanley31

2. When you're up to your neck in alligators, sometimes you forget that your mission is to drain the swamp. barrystanleywww.barrystanleyfasd.comdocstocbstanley 31

3. Historical view of prenatal alcohol and FASD Aristotle - 384-322 B.C. Diogenes - cir. 400 B.C. Plutarch- 45-125 A.D. Behold, thou shalt conceive and bear a son: And now, drink no wine or strong drink. Judges 13:7 Navajo tradition, women who drink crazy water when bearing a child, will give birth to a child crazy in body and mind. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

4. 19th century - 21 references to the effect of PAE 1726- British College of Physicians report to Parliament. ‘a cause of weak, feeble and distempered children. 1834- British House of Commons Commission. ‘starved, shriveled and imperfect look’ 1899- British scientist, Sir Francis Galton. ‘children born to alcoholic mothers were- defective-neurotic.” 1899-Dr. W.C.Sullivan. First scientific study- 120 chronic alcoholic women prisoners-had healthy babies if pregnancy was carried while incarcerated, compared to crippling or lethal birth defects when out of jail. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

5. 20th Century JaquelineRouquette – France. Thesis. Published 1957 Paul Lemoine - French pediatrican. Published 1968 The Lancet . Saturday 9 June 1973 PATTERNS OF MALFORMATION IN OFFSPRING OF CHRONIC ALCOHOLIC MOTHERS Kenneth L. Jones, David W. Smith, Christy N. Ulleland, Ann PytkowiczStreissguth barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

6. 21st Century EPIGENETICS The factor of the mother drinking in a pregnancy NO LONGER STANDS ALONE

7. Opposition and reduced awareness to the consequences of prenatal alcohol • Reaction to prohibition • -Focusing [distracting] on aboriginal populations • Recognition of women’s rights together with society’s ambivalent attitude to alcohol • Post WW11 affluence • Development of the DSM [from 1952]- symptom based • Influence of the alcohol industry barrystanleywww.barrystanleyfasd.comdocstocbstanley 31

8. Nomenclature-1996{Institute of Medicine, Washington, D.C. U.S.A.} • F.A.S- Fetal Alcohol Syndrome. with and without confirmed maternal alcohol exposure. • Partial F.A.S. with confirmed maternal alcohol exposure. • A.R.B.D.- Alcohol Related Birth Defects. with confirmed maternal alcohol exposure. A.R.N.D.- Alcohol Related Neurodevelopment Disorder with confirmed maternal alcohol exposure. F.A.E.- Fetal Alcohol Effects. No longer used. • F.A.S.D.- Fetal Alcohol Spectrum Disorder – includes all the above barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

9. FAS – Only the tip of the iceberg - Fetal alcohol syndrome • - F.A.E. • A.R.N.D. • Alcohol Related Neurodevelopmental Disorder. barrystanleywww.barrystanleyfasd. docstoc bstanley31

10. 1973 FAS – 100%

11. FASD 1996 ARND - 63% FAS – 37% barrystanleywww.barrystanleyfasd.comdocstocbstanley 31

12. FASD 2014 PUBMED 2014 - 4,343 results for publications on “Fetal Alcohol Syndrome” - 3,661 results for publications on “Fetal Alcohol Spectrum Disorder” ARND – 90% FAS – 10%

13. 1996 Report – University of Washington,Seattle , U.S.A. Ann P. Streissguthet.al Understanding the Occurrence of Secondary Disabilities in Clients with Fetal Alcohol Syndrome [FAS] and Fetal Alcohol Effects [FAE] barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

14. Primary Disabilities • -- “are inherent in FASD individuals and are a consequence of the neurological damage and impaired neurological function” {Washington Report. 1996} • affecting • - Cognition and Learning • Memory – all types • Information processing – speed, receiving and conveying • Attention • Perseveration • Adaptive and Executive Functioning • Modulation • Sensory systems • Psychiatric Conditions barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

15. Primary Disabilities show as – or interpreted as - • Stupid • Not caring • Selfish • Attention seeking • Impulsive • Confabulation / Lying • Not interested • Lazy-Learning disabilities at school • Not learning from experience • Poor hygiene. • Difficulty with relationships. • Violent • Boundary issues. • Lonely. • Poor judgment. • Difficulty communicating • Concrete thinking - taking everything literally • Problems planning and organizing • Easily lead • Difficulty abstractions, humor, sarcasm • Difficulty relating cause and effect, anticipating consequences • Difficulty appreciating others’ points of view • Difficulty expressing remorse or taking responsibility • Frustration barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

16. Secondary Disabilities “Individuals with FAS/FAE have a range of secondary disabilities – disabilities that the individual is not born with, and which could be ameliorated with appropriate interventions.” {Washington Report 1996} Dependant living > 85% Problems with employment > 94% Streissuguthet.al. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

17. Understanding the Occurrence of Secondary Disabilities in Clients with Fetal Alcohol Syndrome [FAS] and Fetal Alcohol Effects [FAE]. Final Report, 1996. University of Washington, Seattle, U.S.A. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

18. Myth - FAS is the most severe/worst form of FASD • The terms “severe / worst” need to be qualified. • Truth – • Only approximately 27% of those with FAS will have an I.Q. below 70 – often protected, with fewer secondary disabilities. • 9% of those with ARND will have an I.Q. below 70. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

19. Adaptive Functioning • SIB-R “- an individual’s ability to effectively meet social and community expectations for establishing personal independence, maintaining physical needs, conforming to social norms, and sustaining interpersonal relationships” • Vineland “- the performance of the daily activities required for personal and social sufficiency” barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

20. All those individuals exposed to prenatal alcohol [FASD], FAS and ARND will have permanent inadequate adaptive functioning. Children who have not been exposed to prenatal alcohol may also have inadequate adaptive functioning, that is not permanent. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

21. Developmental stages of 18 year old FASD child! JodeeKulpwww.Betterendings.org

22. ALCOHOL • -use – 12,000 Years • Records negative effects –individual and • society. • Rare references to effects • of PAE – 4,000 years, until • the last 300 years Generations – approx. 600 - 12,000 years 200 – 4,000 years barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

23. ALCOHOL – 2014 • Reflects the historical perspective • Research on alcohol and alcohol related issues • cost – millions annually. • all related to the developed brain. • negligibly less on PAE exposure. • the role of PAE still largely ignored by the alcohol research community, the medical profession and governments. • Pubmed - 2014 • -778,348 results for publications on “alcohol” • - 75,348 results for publications on “alcoholism” • - 3,696 results for publications on “Prenatal Alcohol Exposure” • - 4,343 results for publications on “Fetal Alcohol Syndrome” • - 3,661 results for publications on “Fetal Alcohol Spectrum Disorder” • . • ” barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

24. The Brain and the development of Neurology • ca. 4000 B.C. - Clay tablets from Mesopotamia discuss how to use alcohol to dilute medicine • 460-379 B.C. - Hippocrates states that the brain is involved with sensation and is the seat of intelligence • 335 B.C. - Aristotle writes about sleep; believes heart is seat of mental process • 1543 - Andreas Vesalius discusses the pineal gland and draws the corpus striatum • 1564 - GiulioCesareAranzi coins the term hippocampus • 1587 - GuilioCesareAranzi describes ventricles and hippocampus. He also demonstrates that the retina has a reversed image • 1760 - Arne-Charles Lorry demonstrates that damage to the cerebellum affects motor coordination • 1673 - Joseph DuVerney uses experimental ablation technique in pigeons • 1792 - Giovanni Valentino MattiaFabbroni suggests that nerve action involves both chemical and physical factors • 1838 - Theordor Schwann describes the myelin-forming cell in the peripheral nervous system • 1960 - OlehHornykiewicz shows that brain dopamine is lower than normal in Parkinson's disease patients barrystanleywww.barrystanley.comdocstoc bstanley31

25. The Brain and the development of Neurology Phrenology 19th, 20th, 21st Centuries barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

26. The Brain and the development of Neurology Phineas Gage 1848 19th – 20th Century barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

27. The Brain and the development of Neurology 20th, 21st Centuries • Investigative Tools • - Clinical observation of brain injury/disease • Animal – brain injury/disease • - Brain waves • - Electrical activity • - Neuroimaging • - Scans • - Functional Neuroimaging • - Brain stimulation • Histology • Biochemical • Concepts of Brain Function • - Discrete areas • - Hubs • Generalized • Complex system barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

28. Conectomes, Hubs, Nodes and Axes “Specialization alone, however, cannot fully account for most aspects of brain function. Mounting evidence suggests that integrative processes and dynamic interactions across multiple distributed regions and systems underpin cognitive processes as diverse as visual recognition , language, cognitive control, Emotion, and social cognition”— -- “Abnormal anatomical connectivity and functioning of hub regions has been hypothesized to relate to behavioral and cognitive impairment in several neurological and psychiatric brain disorders.” [ Network hubs in the human brain. Trends in Cognitive Sciences. 2013 ] barrystanleywww.barrystanleyfasd.comdocstocbstanley 31

29. Connectomes, Hubs, Nodes and Axes • Examples • Hypothalamic – Pituitary – Adrenal Axis stress- related autonomic and behavioral reactivity. • Prefrontal Cortex, Hippocampus and Amygdala • Executive functioning, adaptive functioning and stuck-in-set perseveration.

30. The Brain and the development of Neurology 20th, 21st Centuries An accurate description of the human brain – the most complex terrestrial system known - Barry Stanley “A possible definition of a complex system. Acknowledged features of a complex system are the following:
-- the system is composed of a large number of elements; -- the elements are often of different types and have an essential internal structure;
-- the elements are related by nonlinear interactions, often of several different types;
-- the system experiences inputs at several scales.
But I argue that the main hallmark of complex systems is circular causality, namely, the presence of feedbacks of (macroscopic) collective properties and emergent features on the behavior of (microscopic) elements. Elements collectively modify the surroundings, which in turn exerts constraints on them and endow them with different possible states or behaviors. In complex systems, knowing the features and behavior of the single components in isolation is not sufficient to predict the behavior of the system as a whole”. AnnickLesne Multiscale modeling of living systems and their regulation.Proceedings of the Ist Conference CoMMISCo’10 on Mathematics and Computer Modelling of Complex Systems. Institut de recherché pour developpement, Bundy, France. 2010: p13 barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

31. SOME OF THE REGIONS OF THE BRAIN AFFECTED BY PRENATAL ALCOHOL EXPOSURE barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

32. Gross Anatomy barrystanley. www.barrystanleyfasd.com. docstoc bstanley31

33. Brain Size and Cortical Thicknessand the Glial Cell 0ur Brain consists of neurons and glial cells.  Neurons constitue about half the volume of the CNS and glial cells make up the rest.  Glial cells provide support and protection for neurons.  They are thus known as the "supporting cells" of the nervous system.  The four main functions of glial cells are: to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy and remove the carcasses of dead neurons (clean up). The three types of CNS supporting cells are Astrocytes, Oligodendrocytes, and Microglia.  The supporting cells of the PNS are known as Schwann Cells. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

34. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31 Corpus CallosumCallosal Disconnection Syndrome

35. Amygdalae barrystanleywww.barrystanleyfasd.comdocstocbstanley 31

36. Thalamus barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

37. Hypothalamus barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

38. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31 Hippocampus

39. Prefrontal Cortex barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

40. barrystanleywww.barrystanleyfasd.comdocstocbstanley 31 Cerebellum

41. Basal Ganglia barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

42. Cell Structure, Function andNeurotransmitters-some of the effects of PAE barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

43. Neurotrophic Factors and Adult Neurogenesis Proteins that control the development, survival and function of nerve cells [ neurons ] They trigger the development of neurons from progenitor cells Neuronal progenitors persist in the adult brain, but die. Neurotrophic factors might be used to develop those cells for repair of damaged nerve cells. www.barrystanleyfasd.comdocstoc bstanley31

44. Neurotransmitters, Neuromodulator Systems and Hormones • - Dysregulation of Insulin Growth Factors • - NMDA glutamate receptors > synaptic plasticity and memory systems • GABA [a,b,c] gamma-aminobutyric acid > C.N.S. inhibitory [and excitatory during development] neurotransmitter > cell membrane function • - Reduced CholineAcetyltransferase > decreased acetylcholine > Hippocampus > memory – Neuromodulator > platicity, arousal, reward, sensory perceptions and • sustained attention. • Hydroxylase > mood, appetite, sleep, memory, learning • - Decreased Dopamine receptor function > reward learning, reward seeking. Decreased levels of Dopamine in the Prefrontal Cortex, Ventral Tegmental Area • - Hypothalamic-Pituitary Axis > differing activation > stress responsiveness. Male/Female differential stress responsiveness > protective role of estrogens. • Inhibition of Serotonin synthesis and expression of serotonin precursor, tryptophan

45. barrystanleywww.barrystanleyfasd.comdocstocbstanley 31 Hypothalamic-Pituitary-Adrenal Axis

46. DEFINITIONS PRENATAL – Existing or Occurring Before Birth Phenotype - The observable physical or biochemical characteristics of an organism, as determined by both genetics and environment Diagnosis – The identification of the nature of a disease or injury by history, examination and laboratory data. D.N.A. – Double helix molecule Chromosomes , 46 – Storage units for DNA. Genes – Distinct portions of DNA. Determine biological characteristics. Genotype – The genetic makeup of an organism or a group of organisms. GENETICS – The study of heredity and the variation of inherited characteristics. EPIGENETICS – The study of changes in gene function [expression] That do not involve changes in DNA sequence. STEM CELL – develop into specialized cells or replenish some specialized cells- can replicate [ reproduce] indefinitiely. PROGINATOR CELL - more specialized- can only replicate a few times. Nucleic Acids – DNA and RNA Nucleotides – are what the Nucleic Acids are formed from. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

47. barrystanleywww.barrystanleyfasd.comdocstoc bstanley31 Genetics – D.N.A. DNA Structure The long, stringy DNA that makes up genes is spooled within chromosomes inside the nucleus of a cell. (Note that a gene would actually be a much longer stretch of DNA than what is shown here.) DNA consists of two long, twisted chains made up of nucleotides. Each nucleotide contains one base, one phosphate molecule and the sugar molecule deoxyribose. The bases in DNA nucleotides are adenine, thymine, cytosine and guanine.

48. barrystanleywww.barrystanleyfasd.comdocstocbstanley 31 Genetics – R.N.A. Ribonucleic acid [RNA] is a ubiquitous family of large biological Molecules that perform multiple vital roles in the coding, decoding, Regulation, and expression of genes. Together with DNA, RNA Comprises the nucleic acids, which along with proteins, constitute Three major macromolecules essential for all known forms of life.

49. Estimations of the number of Human Genes 1964 – 6,700,000 1990 – 100,000 1993 - 80,000 1994 - 64,000 1996 - 50,000 2004 – 20,000 2009 - 18,877 SOME OF US HAVE MORE GENES THAN OTHERS - BUT MORE IS NOT NECESSARILY BETTER. Pertea and SalzbergGenome Biology 2010, barrystanleywww.barrystanleyfasd.comdocstoc bstanley31

50. How can so few genes determine our diverse biological characteristics? > By small modifications that cause big changes in how the gene works > Called - changes in gene expression >>> Epigenetics barrystanleywww.barrystanleyfasd.comdocstoc bstanley31