anxiety disorders

1. ANXIETY DISORDERS

3. Con�t� Generalized Anxiety Disorder Panic Disorder Phobias � Social Obsessive Compulsive Disorder

4. ANXIETY DISORDERS Panic Disorder with or without Agoraphobia Agoraphobia Specific Phobia Social Phobia Obsessive-Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) (NEXT CLASS) Acute Stress Disorder Generalized Anxiety Disorder (GAD)

5. PANIC ATTACKS Discrete period of intense fear or discomfort in which 4 or more of the following symptoms occur and peak within 10 minutes Accelerated heart rate Sweating Trembling or shaking Shortness of breath

6. Con�t� Feeling of choking Chest pain or discomfort Nausea or abdominal distress Dizzy, unsteady, lightheaded, or faint Feelings of unreality or depersonalization Fear of losing control Fear of dying Numbness Chills or hot flushes

7. ANXIETY Fear: real, immediate danger Anxiety: general or diffuse emotional reation; out of proportion Worry: uncomfortable sequence of negative, emotional thoughts/images; future threats

8. PHOBIAS Persistent and irrational Very specific: object and/or situation Avoidance� � or experiences intense anxiety Can cause serious impairments in occupational and social activities

9. AGORAPHOBIA �fear of marketplace (or places of assembly)� More intense with distance from familiar place or signals of safety Panic attacks �fear of fear� Aware of internal bodily sensations that may signal onset of attach

10. OCD Obsessions: repetitive, unwanted, intrusive cognitive events intrusiveness & diminished control Compulsions cleaning & checking ensure safety of self and others

11. CO-MORBIDITY Various symptoms overlap greatly 50% with one anxiety disorder meet criteria for another Mood Disorders panic disorders with or without agoraphobia agoraphobia OCD

12. Con�t� Substance Abuse 40% patients with substance abuse also meet criteria for at least one anxiety disorder Patients with agoraphobia: self-medication? What about GAD?

13. DIAGNOSTIC CRITERIA Panic Attack: worry about additional attacks Agoraphobia: comfort or security Specific Phobia: cued fear; unreasonable Social Phobia: performance GAD: excessive worry that is difficult to control OCD: must recognize that O&C are unreasonable

14. GENDER DIFFERENCES Women are more likely to suffer from anxiety disorders No differences in: Social phobias OCD

15. GENETIC STUDIES Family studies: twice as common in first-degree relatives high rate of panic disorder in first-degree relatives patients with panic disorder or GAD: relatives have high risk of panic disorder, but not GAD OCD: high rates of anxiety disorders, but not necessarily OCD

16. Con�t� Twin Studies MZ: panic disorder, all phobias, OCD not for GAD, agoraphobia, animal phobias, or social phobia Conclusion: genetic predisposition for anxiety disorders Environmental cues for specific disorders?

17. GAD: Overview GABA/Benzodiazepine Norepinephrine Serotonin CCK CRH & HPA Axis Autonomic Functions Neuroimaging Pharmacotherapy

18. GABA/Benzodiazepine Benzodiazepine: affects action of GABA at GABA receptors; also binds to GABA receptors produce inhibitory postsynaptic potentials anxiolytic: ex. Valium lower number of binding sites for BZ BZs increase in number of receptors reduced sensitivity of receptors

19. NOREPINEPHRINE sympathetic nervous system: fight & flight decreased receptor sensitivity reduced binding sites/receptor ...however: not all studies show abnormalities challenges to show receptor sensitivities changes long-term adaptation?

20. SEROTONIN overactivity of serotonin: initially decrease then overcompensation stimulating postsynaptic receptors: anxiety agonists: hostility & anxiety in GAD reduced serotonin in CSF

21. CCK animal models: CCK agonists & antagonists may interact with other systems serotonin locus coeruleus activity CCK-like compound (pentagastrin): panic attacks panic attacks and GAD?

22. CRH & HPA Axis CRH brain regions = anxiety & fear ex. amygdala activates locus coeruleus: norepinephrine links between stress & anxiety? dexamethasone suppression test � little evidence of link

23. AUTONOMIC FUNCTION reduced skin conductance, increased respiration, increased blood pressure, and reduced heart rate variability diminished flexibility? links to stress? prolonged time for recovery reduced heart rate variability

24. NEUROIMAGING PET Study: elevated metabolism in occipital, temporal, and frontal lobes reduced basal ganglia metabolism increased cerebellar metabolism after BZ treatment: cortical lobes, limbic system, and basal ganglia control group: anxiety scores related to activity in limbic system & basal ganglia

25. PHARMATHERAPY 1. Benzodiazepines most effective for autonomic symptoms 2. Azapirones serotonin: partial agonist fewer withdrawal symptoms 3. Antidepressants drug of choice

26. PANIC DISORDER: OVERVIEW Neuroanatomy Serotonin Norepinephrine GABA/Benzodiazepine

27. NEUROANATOMY earliest neuroanatomical circuit: Gray 1988 septohippocampal brain circuit: brain stem, limbic system, prefrontal cortex drugs: brain stem Cognitive Behavioral Therapy: prefrontal cortex

28. NEUROIMAGING PET studies: exaggerated asymmetry internally cued alarm systems SPECT studies: also exaggerated asymmetry hippocampus & frontal cortex

29. SEROTONIN rostral serotonin system enhanced or diminished? Medial vs. Dorsal Raphe Nuclei Medial: limbic system & prefrontal cortex; modulation of fear & anxiety? Dorsal: many areas; cognitive & motor components?

30. Con�t... Medial RN Dorsal RN SSRIs: highly effective by enhancing serotonin levels unclear how serotonin is abnormal

31. NOREPINEPHRINE role of locus coeruleus outputs to amygdala, BNST, entorhinal cortex, PVN, PAG, lateral hypothalamus input from medulla input mediated by glutamate, CRH, and substance P contains numerous GABA receptors

32. Serotonin & Norepinephrine? SSRI decreases NE = global improvement increasing NE = increases symptoms no correlations between serotonin & norepinephrine metabolites but correlation in healthy volunteers

33. GABA/Benzodiazepine therapeutic effects BZ challenge study: reduced sensitivity of receptors BZ-R antagonists: anxiogenic creates panic in patients, but not in healthy volunteers altered set point?

34. Con�t... reduced BZ binding in occipital, temporal, and frontal cortices PET: generalized reduction in binding orbitofrontal cortex and right insula specific effects in amygdala basolateral nucleus vs central nucleus

35. BEYOND LC/NE... LC activity: inconsistent results high NE metabolites causes panic attacks, but only in subgroup very variable results with agonists & antagonists role in arousal and anticipatory anxiety? indirect role in some symptoms?

36. SOCIAL PHOBIA: OVERVIEW Autonomic Nervous System Respiratory Function Neuroimaging Neuroendocrine Function Social Dominance as a model Serotonin Dopamine

37. Con�t... Non-generalized vs generalized also known as social anxiety disorder

38. AUTONOMIC NS excessive heart rate in certain situations public speaking: non-generalized vs generalized higher levels of NE before and after behavioral challenge not replicated: sympathetic vs parasympathetic nervous systems? little research has been done

39. RESPIRATION CO2 sensitivity is social phobia patients are sensitive to panic-provoking effects of CO2 patients with GAD, OCD, and animal specific-phobias

40. NEUROIMAGING MRI: abnormal cell membrane composition SPECT: dopamine binding is reduced in basal ganglia in generalized social phobia high rates in Parkinson�s patients

41. NEUROENDOCRINE normal dexamethasone suppression and cortisol levels shy children elevated levels of cortisol not into adulthood: no relation to social phobia

42. SOCIAL DOMINANCE animal model social status in baboons: altered HPA axis subordinate baboons: hypercortisolemia not model of social phobia, but consequences of being socially phobic IGF-1: lower stature linked to social phobia

43. Con�t: Social Affiliation roles of oxytocin & vasopressin �Pathways from the hypothalamus to VTA may be critical for integrating social information with reward pathways..� social phobia is not rewarding? Evaluating risks and benefits of social affiliation? But�� look at symptoms

44. SEROTONIN neuroendocrine challenges: only effects on serotonin system serotonin agonist = increase in cortisol social dominance: serotonin agonist increases social status responsive to SSRIs

45. DOPAMINE MOAIs are effective, but not tricyclics PET: abnormalities in dopamine system D2-receptor binding in putamen is related to avoidant personality traits

46. OCD: OVERVIEW Neuroimaging Glutamate & Serotonin

47. NEUROIMAGING abnormalities in striatum increased OCD behaviors are present in patients with basal ganglia disorders increased activity in caudate nucleus related to severity of illness conflicted findings

48. Con�t... MRI: some studies show changes in caudate nuclei volumes related to different methodologies children vs adult OCD patients abnormalities in all pediatric patients reduced striatal volumes: related to symptom severity

49. Con�t... striatal-prefrontal cortex pathways impairment in ability to inhibit context-inappropriate emotional responses lesions of anterior cingulate cortex MRI: no generalized differences, but specific differences in orbitofrontal cortex

50. Con�t... Thalamus partial thalamotomy increased metabolic rates & regional cerebral blood flow response to treatment increased thalamic volumes; maturation rates

51. Conclusion�. Abnormalities in prefrontal cortex - striatal - thalamic circuitry specific reversal by treatment with SSRIs: normalization of thalamus

52. SEROTONIN & GLUTAMATE interaction between these neurotransmitters caudate nucleus: glutamate inhibition of serotonin by glutamate reduction in caudate glutamatergic concentrations related to severity higher relative levels are related to treatment response (SSRIs)

53. PRESENTATION FORMAT before presentations: symptoms, prevalence & epidemiology, etc. one person: 15 minutes two people: 30 minutes hand in: list of 10 references three questions for exam

54. AUTISM & SCHIZOPHRENIA a good review article on neurobiology of autism: background primary sources: different types of experiments being done ex. With NTs: levels being measured, receptors

55. PERSONALITY DISORDERS review of neurobiology & neuroanatomy: not too many details drugs used to treat: several examples comorbidity: how underlying neurobiological deficits are the same between disorders

56. DRUG ADDICTION describe neural circuit for dependence tolerance, sensitization, and withdrawal: take an example of a drug specific drugs: how it affects behavior classical conditioning: describe generally and then how heroin can be conditioned

57. GENERAL POINTS Do not just list studies: integration can give some details on specific studies regarding methodology if interesting Remember: goal is to teach how these factors affect BEHAVIOR and SYMPTOMS�.