Epigenetics, Stress and the Brain Epigenetics Andrew Z. Fire and Craig C. Mello won the Nobel prize in Medicine and Physiology in 2006 for their discovery of "RNA interference gene silencing by double-stranded RNA. This work was first published in 1998. The Epigenome http://genes2brains2mind2me.com/ 2009/12/16/epigenetics-and-cognitivedevelopment-quick-sketch-overview/ http://learn.genetics.utah.edu/content/ epigenetics/inheritance/ Stress Prenatal Stress & Special Needs Students Epigenetics & Prenatal Stress The effects of maternal adversity on foetal growth is mediated by adrenal glucocorticoids (stress hormones) and environmental adversity alters maternal physiology,which then programs HPA activity in the offspring." 1
Stress There is a large body of research in psychology and psychiatry documenting a relationship between both prenatal stress and life events and emotional and behavior disorders in adolescents and adults. In adults the magnitude of the event seems to be important. In adolescents the number of events appears to be important. Life Events Life Events Predisposing factors in a population of adolescent suicide completers. Factor Incidence Chronic medical or psychiatric condition 31.8% Major loss or life event 25% Previous psychiatric diagnosis 22% Drug or alcohol addiction 19% Social problems 16% Hospitalizations - medical and/or psychiatric 10% Relative or friend who died 10% Chronic physical medical problems 9.7% Relative who committed suicide (McBride, Siegel & Duckworth, 1998). 4.8% Life Events In 75.6% of the cases there were readily identifiable precipitating factors or stressful life events noted in the month immediately preceding the suicide. Precipitating factors in a population of adolescent suicide completers. Factor Incidence Epigenetics HPA Axis Fight or flight Family problems (fight with parents) 32% Relationship problems (fight with girl/boyfriend) 31% Legal problems (court appearance, charges) 16% School problems (failed test, upcoming exam) 12% Money problems 2% Prenatal Stress Both human and animal studies have found significant relations between prenatal stress and post natal problems in a variety of behavioral domains, such as attention, language, and learning (see reviews by Mulder et al., 2002; Weinstock, 1997)." A prospective longitudinal study of children by Buitelaar et al. (2003) found significant associations between prenatal stress and infants cognitive development." Prenatal Stress & Autism Two retrospective studies have reported that mothers of ASD children experienced significantly more stressful life events prenatally - 44.7 vs 25.9 than mothers of healthy children. (Beversdof et al., 2005, Ward, 1990). Kinney (2008) found ASD prevalence increased significantly with the severity of prenatal storm exposure. Particularly during months 5-6 and 9-10. 2
Prenatal Stress & Depression "Watson et al. (1999) compared 611 high school seniors who had been prenatally exposed to a severe, magnitude 7.8 earthquake in Tangshan, China in 1976, to 604 matched controls students who were born exactly 1 year after the students in the exposed group. The rate of severe depression was significantly higher in the exposed group (13.3%) than in the control group (5.5%) (p<0.001). Prenatal Stress & ADHD A significant association between prenatal stress and increased risk for attention deficit/ hyperactivity disorder (ADHD) was found in two prospective longitudinal studies." Higher levels of both individual ADHD symptoms and a diagnosis of ADHD were associated with more prenatal exposure to stress (p<0.01),with a stronger effect found for males. (Van den Bergh & Marcoen, 2004; Rodriguez & Bohlin, 2005)." Prenatal Stress & EBD Several studies with children have reported an association between prenatal stress and increased risk of emotional and behavioral problems. (O Connor et al., 2003)." This association held even after controlling for postnatal maternal anxiety, obstetric complications, and family psychosocial disadvantage. Similar effects were found when the children were 4 and 7 years old, suggesting that the effects of prenatal stress were quite persistent." Prenatal & Language Development Prenatal exposure to a high level of objective, storm-caused stress was associated with significantly poorer language test performance at age 2 years. (Laplante et al., 2004)" Neuropathology In reviewing MRI studies of brain anatomy of patients with AD, Brambilla et al (2003) concluded that the most consistently replicated findings included structural abnormalities of the cerebellum and corpus callosum. " Similarly,Eigsti and Shapiro (2003) concluded that a cerebellar abnormality was the most consistent neuropathological finding in histological studies of post-mortem brain tissue in AD." Jay Giedd, in twin studies, found that the cerebellum appears to be most vulnerable to environmental influences (2008)." 3
Bias to Threat Individuals who are anxious have overactive amygdalas which causes them to notice the negative rather than the positive in situations and events. This can be innate or learned. Individuals with a past history of trauma are more likely to develop PTSD when exposed to another trauma. Interventions http://www.mindhabits.com Beversdorf,D.Q.,Manning,S.E.,Hillier,A.,Anderson,S.L.,Nordgren,R.E.,Walters,S.E.,etal.,2005.Timing of prenatal stressors and autism. Journal of Autism and Developmental Disorders35(4),471" Ward,A.J.,1990.A comparison andanalysis of the presence of family problems during pregnancy of mothers of autistic children and mothers of normal children. Child Psychiatry and Human Development, 20(4),279-288." Kinney,D.K.,Miller,A.M.,Crowley,D.J.,Huang,E.,Gerber,E., 2008.Autism pre-valence following prenatal exposure to hurricanes and tropical storms in Louisiana. Journal of Autism and Developmental Disorders38(3),481-488." 4
DennisK.Kinney,DavidJ.Crowley,AndreaM.Mille. (2008). Prenatal stress and risk for autism. Neuroscience and Biobehavioral Reviews 321519-1532." Watson, J.B., Mednick, S.A., Huttunen, M., Wang, X. (1999). Prenatal teratogens and the developmen of adult mental illness. Development and Psychopathology 11(3), 457-466." Mulder, E.J., Robles de Medina, P.G., Huizink, A.C., VandenBergh, B.R., Buitelaar, J.K., Visser, G.H., (2002). Prenatal maternal stress: effects on pregnancy and the (unborn) child. Early Human Development, 70(1-2), 3-14." Weinstock, M., (1997). Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis? Neuroscience and Biobehavioral Reviews, 21(1), 1-10." VandenBergh, B.R., Marcoen, A. (2004). High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Development, 75(4), 1085-1097." Rodriguez, A., Bohlin, G., (2005). Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? Journal of Child Psychology and Psychiatry, and Allied Disciplines, 46(3), 246-254." O Connor, T.G., Heron, J., Golding, J., Glover, V., ALSPAC Study Team. (2003). Maternal antenatal anxiety and behavioural/ emotional problems in children: a test of a programming hypothesis. Journal of Child Psychology and Psychiatry, and Allied Disciplines. 44(7),1025-1036." Laplante, D.P., Barr, R.G., Brunet, A., Galbaud du Fort, G., Meaney, M.L., Saucier, J.F., et al., (2004). Stress during pregnancy affects general intellectual and language functioning in human toddlers. Pediatric Research, 56(3),400-410." Buitelaar, J.K., Huizink, A.C., Mulder,E.J., de Medina, P.G.,Visser, G.H., (2003). Prenata stress and cognitive development and temperament in infants. Neurobiology of Aging, 24(Suppl.1), S53- S60. " Brambilla, P., Hardan, A., di Nemi, S.U., Perez, J., Soares, J.C., Barale, F., 2003. Brain anatomy and development in autism: review of structura MRI studies. Brain Research Bulletin 61(6), 557-569." Dandeneau, S. D., Baldwin, M. W., Baccus, J. R., Sakellaropoulo, M., & Pruessner, J. C. (2007). Cutting stress off at the pass: Reducing vigilance and responsiveness to social threat by manipulating attention. Journal of Personality and Social Psychology, 93, 651-666. The Inhibition of Socially Rejecting Information Among People with High versus Low Self-Esteem: The Role of Attentional Bias and the Effects of Bias Reduction Training in the Journal of Social and Clinical Psychology, 2004, Volume 23, pp. 584-602. 5