Ica March 23 Oxytocin, Social Phobia, Autism

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Ica March 23 Oxytocin, Social Phobia, Autism

  1. 1. Role of Oxytocin in Autism and Social Phobia PSYC 342 Dr JC Pruessner Karen Falcicchio, Chelsey Lam,Yoojung Lee, Candice Lee Kit, Emma Vallance
  2. 2. Oxytocin (OT) • Neuropeptide hormone synthesized in hypothalamic nuclei & secreted by posterior pituitary • Peripheral (hormonal) actions, and actions in brain mediated by specific, high affinity oxytocin receptors
  3. 3. Oxytocin • Established role lactation, labour and birth • Animal models support the involvement of oxytocin in maternal affiliative behaviors (i.e., licking and grooming) • Role in human maternal affiliative behaviors, trust and attachment • Oxytocin may have an important role in the regulation of social behaviors, emotional reactivity and repetitive behaviors
  4. 4. Oxytocin, Autism & Social Phobia? • Given that oxytocin is involved in the regulation of repetitive and affiliative behaviours, and that these are key features of autism, it is believed that oxytocin may play a role in autism and that oxytocin may be an effective treatment for these two core symptom domains • Studies of individuals with social phobia/ social anxiety disorder suggest a possible role for oxytocin as a facilitator of social behavior, an effect which may not be fully utilized in individuals with severe social anxiety
  5. 5. What is Social Phobia?
  6. 6. Feelings & Symptoms • Blushing • Clammy Hands • Difficulty Talking • Nausea • Stomach • Weeping Discomfort • Profuse Sweating • Tantrums • Palpitations • Shaking • Trembling
  7. 7. Common Characteristics • Fear of social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others • Exposure to the feared social situation provokes anxiety • The person recognizes that the fear is excessive or unreasonable. • The situations are avoided or else are endured with intense anxiety or distress
  8. 8. Everyday fear or something more serious?
  9. 9. The Extra Step Faced by Social Phobics • Heightened anxiety levels to the point of avoidance • Advance worry of the social situation days to weeks before • Interpretation of natural fear response cues as dangerous • Avoid forming/maintaining close relationships • Turn down chances to advance their careers • Selective Mutism • Housebound
  10. 10. Why Do Some People Develop Social Phobia? • A person's biological/cognitive makeup • No one gene implicated, but genetic and hormonal disposition predisposes an individual to specified characteristics • Heriditary: Pedigree shows that first-degree relatives of probands with social phobia are 3 times more likely to develop than controls [Bernstein et al.] • Behaviors learned from role models • Overprotective parent • Shy parent • Life events and experiences • Born with a cautious/inhibited nature due to stressful experience in early life • Teased or bullied
  11. 11. Cognitive/ Neurobiology Aspect • Increased activation of amygdala • Sensitization of the HPA axis stress response • Studies by Bernstein et al. show that very low weight (600-1250 g) babies may be at higher risk due to abnormalities in the uncinate fasciculus, (white matter tract connecting the frontal cortex to the amygdala, and other limbic temporal regions)
  12. 12. Prevalence • THIRD largest psychological disorder in United States • Prevalence rates vary widely because of its vague diagnostic criteria and its overlapping symptoms with other disorders • Onset of social phobia typically occurs between 11 and 19 years of age • Male : Female ratio being 2:3 in general population, but clinical ratio is higher for men than women
  13. 13. Comorbidity • Schizophrenia • Acute Stress Disorder • Suicidal/ Homicidal Ideation • Substance Abuse • Panic Disorder • Generalized Anxiety Disorder (GAD) • Depression • Autism Spectrum Disorder
  14. 14. What is Autism?
  15. 15. What is Autism?
  16. 16. Autism Spectrum Disorder From the DSM-IV TR • Social and Communication Deficits • Fixated Interests and Repetitive Behaviors • Symptoms must be present in early childhood
  17. 17. Prevalence • 1 in 166; 68/day; 3/hour • Present cross-culturally and cross-nationally • Found at all income levels • 4:1 male to female ratio • 10:1 male to female ratio in “high functioning” ASD (Autism Spectrum Disorder)
  18. 18. Characteristics I • Impairments in Social Interaction • Expressive non-verbal behavior • Joint Attention • Social “mind” and reciprocity • Communication: speech and language • Echolalia and other repetitions • Poor pragmatic use of language
  19. 19. Characteristics II • Behavioral Symptoms • Repetitive patterns of interests • Self stimulation • Restricted interest • Preoccupation with parts of objects • Cognitive Aspects • Deficit in abstraction • Lack of “Theory of Mind”
  20. 20. Biological Aspects • Lower levels of serum oxytocin compared to controls • Higher levels of oxytocin precursor levels • Autism has been associated with specific variants of the oxytocin receptor genes (Petrovic et al., 2008) • Heightened amygdala activation (faces with a direct gaze)
  21. 21. Feelings • A common myth: Do autistics feel emotion at all? • Missing emotions: • Romantic love • Grief • Expressing emotions: • Through writing • Improves with age
  22. 22. The Autism Spectrum • The Autism Spectrum • Characterized by widespread abnormalities of social interactions and communication, as well as severely restricted interests and highly repetitive behavior • Evidence for dimensional spectrum: • Severity of symptoms vary • Any level of IQ possible • Presence of traits in close relatives
  23. 23. The Autism Spectrum • Autism • Asperger’s Syndrome • Similar to Autism but no significant delay in language development • PDD-NOS (Pervasive Developmental Disorder Not Otherwise Specified) • “Atypical Autism” - most common and somewhat milder than Autism
  24. 24. What could the mechanism be by which variations in Oxytocin could have an effect on autism and social phobia?
  25. 25. Quick Review: Social Stress • HPA axis is highly responsive to psychosocial stress • Main hormones involved: CRF, ACTH, Cortisol, Epinephrine • Regulates fight or flight response and increases alertness to cope with stress
  26. 26. Quick Review: Social Fear 1. a) Sensory information is process in the thalamus b) Pre-frontal cortex 2. Amygdala is activated and projects to brainstem 3. Fear response (similar to stress response) • Research using fearful faces as a cue for social fear can activate the amygdala (seen in fMRI)
  27. 27. Role of Oxytocin in Stress & Fear A) Oxytocin in CNS • Oxytocin has receptors in the limbic system (amygdala) • has an inhibitory effect Evidence: • Intranasal oxytocin + social stimulus (emotional faces, measured by fMRI) showed decreased amygdala activation (Kirsch et al., 2005)
  28. 28. Role of Oxytocin in Stress & Fear • Activation of amygdala and brain stem connection also significantly decreased (Kirsch et al., 2005) Text • Conclusion: Increased oxytocin inhibited the social fear response
  29. 29. Role of Oxytocin in Stress & Fear B) Peripheral Oxytocin: • During social stress, oxytocin was found to inhibit secretion of ACTH, cortisol & catecholamines (ex. epinephrine) • Protective factor because it facilitates approach behavior and inhibits overactivation of HPA axis • Oxytocin increases the ability to interact socially
  30. 30. Oxytocin & Social Phobia • One study found that when given intranasal oxytocin normal individuals showed decreased levels of cortisol in response to social stress vs. controls • Oxytocin seems to promote social behavior by reducing stress and anxiety when presented with social situations • The regulation by oxytocin of the HPA axis may be dysfunctional in individuals with social phobia • May lead to the large increase in stress and anxiety in social situations seen with people suffering from social phobia
  31. 31. Oxytocin & Autism • Hypothesis of autism = increased social fear and social deficits due to increased regulation of fear response by oxytocin
  32. 32. Autism Studies • Several studies have linked specific characteristics and behaviors of autism with oxytocin levels 1. Affective Mind Reading 2. Emotional significance to speech intonation 3. Repetitive behaviors (Heinrichs and Gaab)
  33. 33. Andari et al., 2010 • High functioning autism spectrum disorders were given oxytocin intranasally • Played a virtual game of ball toss with 3 virtual players (social, neutral, antisocial) • Visual face scanning task • Results: • Increased ability to process socially relevant cues • Increased time gazing at the face, specifically the eyes, and decreased number of saccades
  34. 34. What other hormones are involved in Social Phobia and Autism?
  35. 35. Cortisol • Shy children and children with behavioral inhibition typically have higher cortisol levels (Stein, 1998) • Many studies have shown that cortisol levels of individuals with social phobia are normal compared to controls’, whether measuring using urinary free cortisol, plasma cortisol or dexamethasone suppression tests (Bell, Malizia & Nutt, 1999) • Suggests that HPA activity is normal in people with social phobia at the level of cortisol
  36. 36. Growth Hormone (GH) • Stabler et al., reported a striking incidence of social phobia (38%) in individuals with GH deficiency who were treated with GH during childhood • Trancer, Stein & Uhde (1996), discovered that people with social phobia have blunted GH response • Implies central non-adrenergic dysfunction → elevated noradrenaline leads to down regulation of GH • Hypothesis: People with social phobia have lower GH - Two possible explanations: • Presence of social phobia leads to GH deficiency • GH deficiency leads to increased risk of developing social phobia
  37. 37. ACTH • Buitelaar et al. (1992): Autistic children treated with a synthetic analog for ACTH for 4 weeks. • Increased amount and improved quality of social interaction (more eye contact, mutual smiling, and decrease in stereotyped behaviours). • Tordjman et al. (1997): Measured ACTH in autistic adults and children compared to controls.
  38. 38. ACTH • Found higher plasma levels of ACTH in the autistic group compared to controls. • Could be due to chronic hyperarousal, or acute hyperarousal in response to stress, or both • Researchers believe the second to be true, because many studies have reported normal baseline functioning of the HPA axis.
  39. 39. Testosterone • Extreme Male Brain Theory: Autism as an extreme manifestation of some sexually dimorphic traits • Testosterone, 2D:4D & Autism • Males have lower 2D:4D than females • De Bruin (2006): Males with ASD have lower 2D:4D than unaffected individuals • Manning (2001): Siblings and parents of autistic individuals have lower 2D: 4D than unaffected males
  40. 40. Testosterone • Knickmeyer et al. (2005): Analysed fetal testosterone via amniocentesis of 58 children. When they were age 4, their mothers completed a questionnaire assessing language, quality of social relationships, and restricted interests. • Girls scored better on measures of social relationships, and it was related to fetal testosterone levels. • Boys had more restricted interests, and it was related to fetal testosterone levels. • No differences in language, which could reflect a type II error, or an age effect.
  41. 41. Conclusions • Oxytocin is a neuropeptide hormone that plays an important role in the regulation of social behaviors • Autism and Social Phobia are disorders characterized by poor social functioning • Individuals with these disorders appear to have abnormalities in oxytocin at the level of the amygdala and HPA axis which may contribute to the etiology of the symptoms • Although oxytocin appears to play a central role, there are several other hormones that may be involved
  42. 42. Questions?
  43. 43. References • Alcohol Research and Health. Sarah W. Book, Carrie L. Randall. Social anxiety disorder and alcohol use. Retrieved February 24, 2006. • Andari, Elissar, Jean-René Duhamel, Tiziana Zalla, Evelyn Herbrecht, Marion Leboyer, and Angela Sirigu. "Promoting Social Behaviour with Oxytocin in High Functioning Autism Spectrum Disorders." Proceedings of the National Academy of Sciences 107.9 (2010): 4389-394 • Bell, C. J., Malizia, A. L., & Nutt, D. J. (1999). The neurobiology of social phobia. European Archives of Psychiatry and Clinical Neuroscience, 249, S11-S18. • Bernstein, Bettina. Social Phobia. Oct 26, 2009 http://emedicine.medscape.com/article/290854-overview • Bertz, JA, and E. Hollander. "Oxytocin and Experimental Therapeutics in Autism Spectrum Disorders." Prog Brain Res. (2008): 451-62. NCBI. Web. <http://www.ncbi.nlm.nih.gov/pubmed/18655901? ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_MultiItemSupl.Pubmed _TitleSearch&linkpos=1&&log$=pmtitlesearch4>. • Buitelaar, J. K., van Engeland, H., de Kogel, K. H., de Vries, H., van Hoff, J. A. R. A. M., & van Ree, J. M. (1992). The Use of Adrenocorrticotrophic Hormone (4-9) Analog ORG 2766 in Autistic Children: Effects on the Organisation of Behaviour. Biological Psychiatry, 31, 1119-1129. • Condren, R. M., A. O'Neill, et al. (2002). "HPA axis response to a psychological stressor in generalised social phobia." Psychoneuroendocrinology 27(6): 693-703. • Constable RT, Ment LR, Vohr BR, Kesler SR, Fulbright RK, Lacadie C, et al. Prematurely born children demonstratewhite matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects. Pediatrics. Feb 2008;121(2):306-16. • de Bruin, E. I., Verheij, F., Wiegman, T., & Ferdinand, R. F. (2006). Differences in finger length ratio between males with autism, pervasive developmental disorder–not otherwise specified, ADHD, and anxiety disorders. Developmental Medicine & Child Neurology, 48, 962-965. • Early Signs of Autism- Stacking Blocks, No Eye Contact. Dir. Unknown. Early Signs of Autism- Stacking Blocks, No Eye Contact. Youtube, 20 Nov. 2006. Web. 22 Mar. 2010. <http://www.youtube.com/watch? v=q7e4_Of8CbU&feature=related>.
  44. 44. References • Guastella, Adam J., Alexandra L. Howard, Mark R. Dadds, Philip Mitchell, and Dean S. Carson. "A Randomized Controlled Trial of Intranasal Oxytocin as an Adjunct to Exposure Therapy for Social Anxiety Disorder." Psychoneuroendocrinology 34.6 (2009): 917-23. • Heinrichs, Markus, and Jens Gaab. "Neuroendocrine Mechanisms of Stress and Social Interaction: Implications for Mental Disorders." Current Opinion in Psychiatry 20 (2007): 158-62. • Hoge, EA, MH Pollack, PJ Zak, and NM Simon. "Oxytocin Levels in Social Anxiety Disorder." CNS Neurosci Ther. (2008): 165-70. Web. <http://www.ncbi.nlm.nih.gov/pubmed/18801109>. • Kirsch, Peter, Christine Esslinger, Qiang Chen, Daniela Mier, Stephanie LIs, Sarina Siddhanti, Harald Gruppe, Venkata S. Mattay, Bernd Gallhofer, and Andreas Meyer-Lindenberg. "Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans." The Journal of Neuroscience 25.49 (2007): 11489-1493. • Knickmeyer, R., Baron-Cohen, S., Raggatt, P., & Taylor, K. (2005) Foetal testosterone, social relationships, and restricted interests in children. Journal of Child Psychology and Psychiatry, 46(2), 198-210. • Manning, J. T., Baron-Cohen, S., Wheelwright, S., & Sanders, G. (2001). The 2nd to 4th digit ratio and autism. Developmental Medicine & Child Neurology, 43, 160-164. • Petrovic, Predrag, Raffael Kalisch, Tania Singer, and Raymond J. Dolan. "Oxytocin Attenuates Affective Evalutations of Conditioned Faces and Amygdala Activity." The Journal of Neuroscience 28.26 (2008): 6607-615. • pp. 29–30. Social Phobia: Diagnosis, Assessment, and Treatment. Richard G. Heimberg. Guilford Press • Rapee RM, Heimberg RG (August 1997). "A cognitive-behavioral model of anxiety in social phobia". Behav Res Ther 35 (8): 741–56. doi:10.1016/S0005-7967(97)00022-3. PMID 9256517. • Schwartz C, Snidman N, Kagan J (1999) Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry 38:1008-1015
  45. 45. References • Smith, Joel. "This Way of Life: Expressing and Feeling Emotions." Review. This Is the Way of Life. Joel Smith, 2007. Web. 22 Mar. 2010. http://thiswayoflife.org/feelings.html • Stabler, B., Tancer, M. E., Ranc, J., & Underwood, L. E. (1996). Evidence for Social Phobia and Other Psychiatric Disorders in Adults Who Were Growth Hormone Deficient During Childhood. Anxiety, 2, 86-89. • Stein, M. B. (1998). Neurobiological Perspectives on Social Phobia: From Affiliation to Zoology. Biological Psychiatry, 44, 1277-1285. • Stein MB, Goldin PR, Sareen J, Zorrilla LT, Brown GG. Increased amygdala activation to angry and contemptuous faces in generalized social phobia. Arch Gen Psychiatry. Nov 2002;59(11):1027-34. • Tancer, M. E., Stein M. B., & Uhde, T. (1993). Growth Hormone Response to Intravenous Clonidine in Social Phobia: Comparison to Patients with Panic Disorder and Healthy Volunteers. Biological Psychiatry, 34, 591-595. • Tordjman, S., Anderson, G. M., McBride, P. A., Hertzig, M. E., Snow, M. E., Hall, L. M., et al. (1997). Plasma β- Endorphin, Adrenocorticotropin Hormone, and Cortisol in Autism. Journal of Child Psychology and Psychiatry, 38(6), 705-725. • Unknown. "Autistic Disorder." DSM-5 Development. American Psychiatric Association, 2010. Web. 22 Mar. 2010. http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=94 • Unknown. "Autism Spectrum Disorders (Pervasive Developmental Disorders)." National Institute of Mental Health. U.S. Department of Health and Human Services, 18 Mar. 2010. Web. 22 Mar. 2010. http://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-pervasive-developmental-disorders/ index.shtml • Unknown. "Early Signs of Autism - Detecting Pre-Autism Symptoms." Parent Infant Clinic. Infant Mental Health, 2008. Web. 22 Mar. 2010. <http://www.infantmentalhealth.com/early_signs_of_autism.htm> • http://counsellingresource.com/distress/anxiety-disorders/social-phobia-symptoms.html

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