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Anxiety: clinical

Anxiety: clinical. April 2, 2019. Anxiety Disorders. Anxiety Disorders. Excessive fear/anxiety response to stimuli that do not normally evoke such a response Physiologic (autonomic arousal) E motional (fear, marked distress) Cognitive (anticipation, rumination, distractibility)

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Anxiety: clinical

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  1. Anxiety: clinical April 2, 2019

  2. Anxiety Disorders

  3. Anxiety Disorders • Excessive fear/anxiety response to stimuli that do not normally evoke such a response • Physiologic (autonomic arousal) • Emotional (fear, marked distress) • Cognitive (anticipation, rumination, distractibility) • Behavioral (avoidance/endured with distress) • Classified by evoking object/situation • Frequent and persistent • Interferes with role or function

  4. ANXIETY DISORDERS • High prevalence: affect 350 million people worldwide (~5%); up to 30% suffer at some point • Include: phobias • separation anxiety disorder • generalized anxiety disorder (GAD) • panic disorder • obsessive-compulsive disorder (OCD) • post-traumatic stress disorder (PTSD) • Common link: excessive fear in the absence of danger that can be specifically triggered and leads to avoidance

  5. DSM Classification

  6. GENERALIZED ANXIETY DISORDER (GAD) • Essential feature: unrealistic or excessive anxiety & worry about a number of events or activities • Diagnostic criteria: Persistent symptoms for at least 6 mo. • Symptoms: Excessive anxiety • Worries that cannot be controlled • Feeling on edge • Poor concentration, or mind going blank • Physical symptoms: • Restlessness • Fatigue • Muscle tension • Sleep disturbance • Irritability

  7. Panic Attack • Abrupt episode of intense fear or discomfort - peaks in approximately 10 minutes • Includes at least 4 of the following 13 symptoms: • palpitations • nausea or abdominal discomfort • sweating • dizziness or lightheadedness • trembling • a sense of things being unreal • shortness of breath • fear of losing control or "going crazy" • feeling of choking • a fear of dying • chest pain or discomfort; tingling sensations • chills or hot flushes

  8. Panic decreases frontal lobe activity, increases thalamic activity

  9. SOCIAL ANXIETY DISORDER (SAD) • Characterized by intense, irrational fear of being negatively evaluated in at least 1 social or performance situation • Exposure to feared circumstance provokes immediate panic attack • Patient may recognize the excessive fear, but cannot overcome it • Mean age of onset: mid-teens • Hypersensitive amygdala, PFC, ACC • ACC can perceive social exclusion as physical pain in social anxiety patients

  10. Post-Traumatic Stress Disorder (PTSD) • Exposure to severe threat (death, severe injury, violence) • ≥ 1 recurrent, distressing intrusions re: event • involuntary memories • dreams • waking re-experience (flashback) • psychological or physiologic distress in response to reminders • Persistent avoidance of reminders of event • ≥ 2 alterations in emotions/cognition • amnesia for aspects of event (dissociation) • negative expectations about self and world • emotional changes (detachment, guilt/shame, loss of interest/positive emotions) • ≥ 2 alterations in physiologic arousal/reactivity • Irritability - Disturbance of sleep • Hypervigilance - Poor concentration • Exaggerated startle - Reckless or self-destructive behavior

  11. Post-Traumatic Stress Disorder (PTSD) Neuroanatomical/functional changes in PTSD: smaller HPC, ACC volumes increased amygdala activity decreased medial PFC/ACC function increased cortisol levels, NE responses to stress Treatments effective in animal studies of PTSD result in: Increased neurogenesis Enhanced memory Increased hippocampal volume

  12. PTSD patients exposed to emotionally negative images have hyperactive amygdala response TENP: trauma-exposed, non-PTSD Neut, neutral images Brohawnet al, Biol Psychiatry. 2010;68:1023-1030

  13. Obsessive-Compulsive Disorder • Obsessions • Persistent ideas, thoughts, impulses, or visual images that are experienced as intrusive and senseless • recognized as product of his/her mind (vs. delusions) • attempts to ignore/suppress/neutralize them with other thought or action • or Compulsions • repetitive, purposeful, and intentional behaviors performed usually in response to an obsessive thought • performed according to certain rules or in a repetitive, stereotyped fashion • designed to neutralize or to prevent discomfort (anxiety) of some dreaded event or situation • not always connected in a realistic way with what it is designed to prevent • Recognized as excessive or unreasonable • Cause marked distress, are time consuming or interfere with normal routine and functioning

  14. OCD Symptom Factors

  15. Risk Factors for Anxiety Disorders • Biological • genetics • inhibited temperament • evolutionary history Mineka, 2006 Magee, 1999

  16. Genetics of Anxiety Disorders • No autosomal genes suggested or identified • Non-Mendelian, complex inheritance pattern • Linkage/association studies • 12 loci for potential genes on various chromosomes • Most studies have failed replication in independent samples • Suggests environmental interaction with multiple predisposing genes (e.g., s/s SERT) Domschke, 2010

  17. Heritability of Neuropsychiatric Disorders Bienvenu, 2011

  18. Environmental Risk Factors • Learning History • Vicarious learning • Mastery • Family history of chronic illness • Trauma exposure • Relative sexual abuse (social anxiety with onset < 12 yrs) • Accident, natural disaster & combat (agoraphobia) • Adult violence/aggression (specific phobias) Mineka, 2006 Magee, 1999

  19. Early Life Stress Interaction with 5-HTTLPR s allele Interaction between having S/S and ELS Nugent, 2011

  20. Behavioral Theory of Anxiety

  21. Classical Conditioning

  22. Operant Conditioning to Improve Punctuality at Work

  23. Conditioning does not Explain…. • How different anxiety disorders are instantiated in the CNS • Variable heritability of anxiety disorders • How CR arises with no history of specific CS/US pairing • Higher incidence/persistence of certain phobias (snakes, spiders, heights, water, closed/open spaces)

  24. Functional Neuroanatomy of Affectively-Mediated Behavior

  25. Neuro-anatomy of Fear Response Garakani, 2006

  26. Cortical Mechanisms Underlying Extinction

  27. Functional Biomarker ? • Increased amygdala responsiveness associated w/ • Exposure to fearful faces • Diagnoses of SAD, PTSD, Panic disorder • Spontaneous panic attacks • Chemically-induced panic attacks in healthy controls • ‘Phobic-prone’ personality • Being a carrier of catecholamine-related polymorphisms • 5-HTTLPR s allele • COMT val158met • BDNF val66met Domschke, 2010

  28. Hariri, 2005

  29. Etkin & Wager, 2007

  30. Etkin & Wager, 2007

  31. vmPFC rACC dACC Insula Amyg. Thal. PTSD Studies Social Anxiety & Specific Phobia Studies Etkin & Wager, 2007

  32. Treatment of anxiety disorders: GAD: Cognitive behavioral therapy (CBT) Anti-depressants (SSRI: 5-HT/SNRI: NE) Anti-convulsants– target GABAR (benzodiazepines, pregabalin) SAD (social anxiety): 4) Oxytocin (NP)– social bonding, lactation, birth (PVN); may not bind to OR (competitive antagonists do not block effects)

  33. Cognitive behavioral therapy (CBT): can be highly effective in treating some forms of anxiety *especially exposure therapy (habituation): patient repeatedly exposed to stimulus until fear subsides Spider phobia: CBT reduced amygdalar activation Goossenset al, Biol Psych 2007;62:1119-1125

  34. Mechanism of action of benzodiazepines (anti-anxiety drugs) -BDZ binding: enhanced GABA binding  increased Cl- entry increased membrane potential  reduced excitability

  35. Barbiturate anti-anxiolytics : bind GABA receptor at different site barbiturates: increased duration of Cl- channel opening benzodiazepines: increased frequency of opening Cl- channel

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