This document summarizes several anxiety disorders including generalized anxiety disorder, panic disorder, phobias, obsessive compulsive disorder, and post-traumatic stress disorder. It discusses the primary symptoms and epidemiology of each disorder. It also outlines several first-line and second-line treatment options, including cognitive behavioral therapy, SSRIs, benzodiazepines, and psychosurgery. Additionally, it reviews several animal models used to study anxiety and the neurochemistry of the GABA and serotonin systems in relation to anxiety disorders.

1. Anxiety Disorders
Brian J. Piper, Ph.D.

2. Primary Objectives
• Disorders • Therapies
– Generalized Anxiety Disorders – Barbiturates
– Panic Disorder – Benzodiazepines
– Phobias – SSRIs
– Obsessive Compulsive Disorder – Others
– Post-Traumatic Stress Disorder • CBT
• Psychosurgery

3. Secondary Objectives
• Neurochemistry • Methods
– GABA – Open-field
– 5-HT – Elevated Plus & Zero Mazes
• Neuroanatomy – Light-Dark Test
– Amygdala – Conflict Test
– Anterior Cingulate Cortex
– Basal Ganglia

4. Terminology
• Fear (current) versus Anxiety (future)
4

5. Anxiety Disorders
 Panic Disorder
 Phobias
 Generalized Anxiety Disorder
 Social Anxiety Disorder
 Obsessive-Compulsive Disorder
 Post-Traumatic Stress Disorder

6. Epidemiology
Kessler et al. (2005). Archives of General Psychiatry, 62, 617-627.

7. Panic Disorder
Panic Attack: discrete period of intense fear, 4+
symptoms develop abruptly and peak within 10
minutes
Individual Differences: multi/day versus 1/week
Agoraphobia: fear of open-spaces
1st 2:30
http://www.youtube.com/watch?v=2gNGUartUEI

8. Phobia
• Marked & persistent fear that is excessive or
unreasonable, cued by presence or
anticipation of object/situation
• The avoidance interferes significantly with
normal routine, occupational or social
activities.
8

9. Kinds of Phobias
Arachonophobia Phobia of spiders.
Acrophobia Phobia of heights.
Claustrophobia Phobia of closed spaces.
Hemophobia Phobia of blood.

10. Systematic Desensitization
Spider
• 1) Create hierarchy of fears ↓
• 2) Relaxation techniques
• 3) Combine
Joseph Wolpe, M.D.
1915-1997

11. Obsessive-Compulsive Disorder
• Obsessions
– 1. Recurrent and persistent thoughts, urges, or
images that are experienced, at some time during
the disturbance, as intrusive and unwanted and
that in most individuals cause marked anxiety or
distress
– 2. The person attempts to ignore or suppress such
thoughts, urges, or images, or to neutralize them
with some other thought or action (i.e., by
performing a compulsion)

12. Compulsions
• 1. Repetitive behaviors (e.g., hand washing, ordering,
checking) or mental acts (e.g., praying, counting,
repeating words silently) that the person feels driven to
perform in response to an obsession, or according to
rules that must be applied rigidly
• 2. The behaviors or mental acts are aimed at
preventing or reducing anxiety or distress, or
preventing some dreaded event or situation; however,
these behaviors or mental acts either are not
connected in a realistic way with what they are
designed to neutralize or prevent, or are clearly
excessive

13. OCD
• 1st Two Minutes:
• http://www.youtube.com/watch?v=44DCWslb
sNM
13

14. Cingulate Cortex
14

15. Anterior Cingulate & OCD
• OCD and controls completed a
difficult continuous
performance test during fMRI.
• OCD > controls in Anterior
Cingulate Cortex
• Target of psychosurgery
15
Ursu et al. (2003). Psychological Science, 14, 347-353.

16. Psychosurgery
1874-1955
• 1949: Antonio Egas Moniz received Nobel
prize for frontal leucotomy
• 1940s-1967: Walter Freeman develops frontal
lobotomy (transorbital)
• Current: lesioning & deep brain stimulation is
a last resort

17. Generalized Anxiety Disorder
DSM-IV-TR Criteria
A. Excessive anxiety and worry (apprehensive expectation),
occurring more-days-than-not for at least 6 months.
B. The person finds it difficult to control the worry.
C. three (or more) of the following six symptoms:
1. Restlessness
2. Being easily fatigued
3. Difficulty concentrating
4. Irritability
5. Muscle tension
6. Sleep disturbance

18. Post-Traumatic Stress Disorder
Four or more weeks of the following symptoms constitute
Post-Traumatic Stress Disorder (PTSD):
Re-experiencing: nightmares, flashbacks, intrusive thoughts
Avoidance: situation & associated
Physical Arousal: sleep, concentration, irritability
Lifetime Prevalence: 5% men, 10% women
Significant social or occupational impairment
:
3 min http://www.youtube.com/watch?v=7aFs6695VyQ

19. PTSD Talk Therapy
• Participant groups matched based on prior trauma
(moderate), sex, and age
• Eye Movement Desensitization & Reprocessing: imagine trauma + follow therapists
rapidly moving finger
• Control: imagine trauma while staring at stationary object (same duration as
experimental
*
*
Dunn et al. (1996). J Behav Therapy Exp Psychiatry, 27, 231-239.

20. Barbiturates
• Barbital synthesized in 1903
• Popular sleep aid until 1950s
• Act on GABAA in limbic system
http://images.google.com/imgres?imgurl=http://pubs.acs.org/cen/img/83/i25/8325pheno_barbara.tifcxd.JPG&imgrefurl=http://pubs.acs.org/cen/coverstory/83/8325/8325phenobarbital.html&h=287&w=156&sz=46&hl=en&sig2=zuAuHA0TzlNEk45oUL1xH
w&start=19&tbnid=heE_tNcgW041OM:&tbnh=115&tbnw=63&ei=bRW0RI6zEMaoaK-a5bAG&prev=/images%3Fq%3Dphenobarbital%26svnum%3D10%26hl%3Den%26lr%3D%26rls%3DCNDB,CNDB:2004-15,CNDB:en

21. Comparison
(Long)
(Short)
(Long)
(Ultrashort)

22. Valium
• Invented by Leo Sternbach and began use in
1963
• Uses: anxiety, insomnia, cocaine OD
1908-2005
• PK: long half life, bioactive metabolites
• PD: Bezodiazepine site on GABAA

23. Animal Models of Anxiety: Elevated
Zero Maze
• Dependent Variable: % Open
Braun et al. (2011). Pharmacol Biochem Behav, 97, 406-415.

24. Benzodiazepine Tolerance
• Mice received
implants to deliver 2
mg/kg/day of
lorazepam.
• Three behaviors were
measured in an open
field.
Fahey et al. (2001). Pharmacology Biochemistry Behavior 69, 1-8 .

25. Cross Tolerance
• The benzodiazepine chlordiazepoxide (CDP) or
diazepam (DZ) impaired tilt-plane
performance.
• Ethanol caused a greater disruption in benzo
naïve rats.
Khana et al. (1998) Pharm Biochem Behav 59, 511-519.

26. Flunitrazepam
• Rohypnol “roofies”
• Half-life: 20 hours
• 5-10 times more potent then valium

27. Self-administration
Opiates > Benzodiazepines > Hallucinogens

28. GABA Receptors
• Receptor is composed
of 5 subunits.
• Binding of GABA results
in influx of Chloride.
• Other drugs also bind to
receptor.
• GABAA & GABAB

29. GABAA
Barbiturates:
open channel
Benzodiazepines
open channel only if GABA
present

30. Light Dark Test
• Dependent Measure: % time in lit area
• Anxiolytic: increased % time in lit area
• Anxiogenic: decreased % time in lit area

31. Light Dark Test
• Role of GABA or 5-HT in anxiety
--------------------------------- --------------------------------------------------

32. Vogel Conflict Test
• Water deprived animals will get mild footshock
for drinking H2O
Basso et al. (2011). Behavioral Brain Research, 218, 174-183.

33. Gamma-hydroxybutyrate
• Georgia Home Boy, Grevious Bodily Harm, Liquid X
• Clear and salty liquid, rave & date rape drug
• Medical uses: Narcolepsy (cataplexy) and anesthetic
• PK: half-life of 40 min
• PD: GABAB & GHB agonist
GABA GHB

34. Forensic Applications
Kintz (2005) J Forensic Sci 28(1), 1-6.

35. Forensic Applications
Kintz (2005) J Forensic Sci 28(1), 1-6.

36. GHB and Behavior
• Flies received GHB by
injection (!).
• GHB increased
immobility in normal
(wild-type) and EtOH
sensitive (Cheapdate)
flies.
• A GABAB antagonist
prevented these
effects.
Dimitrijevic et al. (2005). European J Pharmacol, 519, 246-252.

37. Utility of Multimodal
• Children (ages 7-12, N=488) with one (GAD,
separation anxiety disorder, social phobia:
21.9%), or more anxiety disorders (78.1%) were
randomized to placebo, Cognitive Behavioral
Therapy, sertraline, or sertraline/CBT for 12
weeks.
Walkup et al. (2005) NEJM, 359, 2753-2766.

38. Utility of Multimodal
Improvement
Placebo: 7.0
CBT: 8.1
Sertraline: 9.0
Combo: 12.0

39. But Differential Side-Effects Rates
25 *
20
15
10
5
0
Zoloft - Zoloft +

40. Videocast
• Charney, Dennis S. (2002). Underlieing
mechanisms of Anxiety & Post-Traumatic
Stress. Starts at 04:00 to 36:00
http://videocast.nih.gov/launch.asp?10696

41. Summary
Disorder Adult Adolescent 1st Line Tx 2nd Line Tx
Lifetime % Lifetime %
GAD 5.7 1.0 CBT, SSRI, SSNRI Benzos
Panic Disorder 4.7 2.3 CBT, SSRI
Phobias 12.5 15.1 Systematic
Desensitization
OCD 1.6 - CBT, SSRI Benzos
psychosurgery
PTSD 6.8 4.0 CBT, SSRI EMDR
http://www.nimh.nih.gov/statistics/index.shtml

42. Origins of Anxiety
• Learn: videotapes of fear response to fake snake
or plastic flower
• Test: show a stimuli
Mineka, S. (1985). J Abnormal Psychol

43. Origins of Anxiety
(Susan Mineka)
• Learn: videotapes of fear response to fake snake
or plastic flower
• Test: show a stimuli
• Response: Snake-Fear; Flower- No Fear
• Supports Social-Learning & Evolutionary
Psychology