Neurobiology of Fear and Anxiety

Transcription

1 Neurobiology of Fear and Anxiety Basic and Protective Mechanisms Markus Heinrichs, Ph.D. Albert-Ludwigs University of Freiburg, Germany Department of Psychology, Laboratory for Biological and Personality Psychology Freiburg Brain Imaging Center (FBI), Social Neuroscience Group, University Medical Center Outpatient Psychotherapy Clinic and Research Unit Stress-Related Disorders Role of the Human Amygdala Vytal & Hamann (2010) J Cogn Neurosci Feinstein, Adolphs, Damasio & Tranel (2011) Current Biology 2 1

2 Neural Regions and Circuits Implicated in Fear and Anxiety Amygdala as key structure mediating between brainstem and cortical levels in fear and anxiety B A C A Inflated estimates of threat cost/probability B Increased threat attention/hypervigilance C Deficient safety learning F D Behavioral and cognitive avoidance E D E Heightened reactivity to threat uncertainty F Maladaptive control Grupe & Nitschke (2013) Nat Rev Neurosci 3 Neuroendocrinology of Fear and Anxiety Lightman & Conway-Campbell (2010) Nat Rev Neurosci 4 2

3 Social Stress/Social Anxiety Exposure in Humans Trier Social Stress Test (TSST) Kirschbaum, Pirke & Hellhammer (1993) Neuropsychobiology von Dawans, Kirschbaum & Heinrichs (2011) Psychoneuroendocrinology von Dawans, Fischbacher, Kirschbaum, Fehr & Heinrichs (2012) Psychological Science 5 Cortisol Response to Psychosocial Stress STRESS Breast-Feeding Holding Heinrichs, Meinlschmidt, Neumann, Wagner, Kirschbaum, Ehlert & Hellhammer (2001) J Clin Endocrinol Metab Rimmele, Costa Zellweger, Marti, Seiler, Mohiyeddini, Ehlert & Heinrichs (2007) Psychoneuroendocrinology 6 3

4 Induction of social stress/ social anxiety Healthy Controls Social Phobia Soravia, de Quervain & Heinrichs (2009) Biol Psychology Soravia, Heinrichs et al. (2006) Proc Natl Acad Sci 7 Positive Social Interaction as Protective Factor Positive social interaction (e.g., social support) exerts powerful protective effects against fear, anxiety, and stress (Cohen et al., 1997, JAMA; Baumgartner, Heinrichs et al., 2008, Neuron; Ditzen & Heinrichs, 2013, Restor Neurol Neurosci; Heinrichs et al., 2003, Biol Psychiatry; Heinrichs et al., 2005, Am J Psychiatry; Heinrichs & Domes, 2008, Prog Brain Res; Heinrichs & Gaab, 2007; Curr Opin Psychiatry; House et al., 1988, Science; Soravia, Heinrichs et al., 2006, Proc Natl Acad Sci; Williams et al., 1992, JAMA; von Dawans et al., 2012, Psychol Sci) What are the underlying mechanisms of the protective effects of social interactions? 8 4

5 Oxytocin and Autonomic Fear Response Huber, Veinante & Stoop (2005) Science Viviani, Charlet, van den Burg, Robinet, Hurni, Abatis, Magara & Stoop (2011) Science 9 Oxytocin Homologs Donaldson & Young (2008) Science 10 5

6 Of Mice and Men 11 Oxytocin in the Human Brain 12 6

7 Oxytocin in the Human Brain Meyer-Lindenberg, Domes, Kirsch & Heinrichs (2011) Nat Rev Neurosci 13 Neuropeptides Enter the Brain after Intranasal Administration in Humans (CSF) Born et al. (2002) Nat Neurosci Heinrichs et al. (2004) Physiol Behav 14 7

8 Structure of the Oxytocin Receptor and its Interaction with the Ligand Zingg & Laporte (2003) Trends Endocrinol Metab 15 Oxytocin and Social Stress Buffering Oxytocin vs. Placebo (intranasally double-blind) Mood Anxiety Introduction Social Support vs. Alone Trier Social Stress Test Mood Anxiety Time (min) = Saliva Samples 16 8

9 Oxytocin and Social Stress Buffering STRESS Heinrichs et al. (2003) Biol Psychiatry 17 Oxytocin Attenuates Amygdala Reactivity to Fear in Social Phobia Labuschagne et al. (2010) Neuropsychopharmacol 18 9

10 Oxytocin Increases Trust by Reducing Fear-Responsive Brain Reactivity PLAC OT PLAC OT Kosfeld*, Heinrichs* et al. (2005) Nature Baumgartner, Heinrichs et al. (2008) Neuron 19 Endogenous Stimulation: Physical Contact IV Catheter Mood Anxiety Introduction Alone vs. Social Support vs. Physical Contact Preparation (alone) Trier Social Stress Test Mood Anxiety Turner et al. (1999) Psychiatry = Plasma Samples Time (min) = Saliva Samples 20 10

11 Cortisol Stress Response and Physical Contact A 30 AUC i Mean Salivary Cortisol, nmol/l No Interaction Social Support Physical Contact 5 No Interaction Social Support 0 Physical Contact Time, min Ditzen, Neumann, Bodenmann, von Dawans, Turner, Ehlert & Heinrichs (2007) Psychoneuroendocrinology 21 Cardiovascular Stress Response and Physical Contact B AUC i No Interaction Social Support Physical Contact Mean Heart Rate, Beats/min 90 No Interaction Social Support Physical Contact Time, min Ditzen, Neumann, Bodenmann, von Dawans, Turner, Ehlert & Heinrichs (2007) Psychoneuroendocrinology 22 11

12 SOCIAL ANXIETY/STRESS Amygdala-Cingulate Circuits Hypothalamic-Pituitary- Adrenal Axis Social Buffering - + Coping PROSOCIAL BEHAVIOR? Social Support Approach Behavior Physical Contact CENTRAL OXYTOCINERGIC SYSTEM Secretion Receptors Genetics + BEHAVIOR THERAPY PSYCHO- BIOLOGICAL THERAPY + OXYTOCIN TREATMENT Heinrichs & Domes (2008) Progress in Brain Research Heinrichs, von Dawans & Domes (2009) Frontiers in Neuroendocrinology HEALTH Meyer-Lindenberg, Domes, Kirsch & Heinrichs (2011) Nature Reviews Neuroscience Kumsta & Heinrichs (2013) Current Opinion in Neurobiology PSYCHO- PATHOLOGY (e.g., Autism, Social Phobia, Borderline Personality Disorder) 23 Acknowledgment Scientific Staff Valentina Colonnello, Ph.D. PD Dr. Gregor Domes Dipl.-Psych. Manuela Kanat Amalie Trüg, M.Sc. Dr. Nicole Ower Dr. Bastian Schiller Marion Schwaiger, M.Sc. Dr. Tobias Stächele Dipl.-Biol. Xenia Steinbach Dr. Bernadette von Dawans Administrative und Technical Staff Julia Albicker, B.Sc. Katharina Glatz, M.Sc. Catrin Angst-Eckert Marlon Grodd, IT Eleonore Brudasca, MTA Judith Grossmann, B.Sc. Birgit Bühren, Admin Ines Spenthof, B.Sc. Rob Falkenstein Julia Werhahn, B.Sc. Olivia Fellinger, Admin 24 12

13 Acknowledgment 25 Biological Psychology and Social Neuroscience Group in Freiburg 26 13