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1
PTSD: Neurobiology
2
Neurophysiologic Alterations in PTSD
• Stress hormone systems - adrenal gland
» Sympatho-adrenomedullary
» Hypothlamic-p...
3
Adrenergic Alterations
• Exaggerated increases in cardiovascular
responses to trauma-specific stimuli
• Increased catech...
4
HPA Axis Alterations
PTSD Major Depression
Cortisol levels Low High
Glucocorticoid receptors Increased Decreased
Dexamet...
Hypothalamus
CRF
Posterior
Pituitary
Anterior
Pituitary
ACTH
Adrenal
Kidney
Norepinephrine ↑
Cortisol ↓
PTSD
6
Stress Hormone Systems
•Norepinephrine – “revving up” hormone
•Cortisol – “quieting down” hormone
•Both hormones are rel...
7
LeDoux, Scientific American, 1994
8
Hiker and Snake
• Immediate response
- Fight or flight
- Quick and dirty
• Delayed response
- Recognition, planning
- Sl...
9
SENSORY CORTEX
SENSORY
THALAMUS
AMYGDALA
EMOTIONAL
STIMULUS
EMOTIONAL
RESPONSES
“High Road”
“Low Road”
10
Why do I get so angry?
What’s wrong with my memory?
• Amygdala
» “Reptile brain, dinosaur brain”
» Emotional response
»...
11
12
13
“Battlemind”
• In a dangerous situation you don’t want to sit around
and think. You want to act immediately using your
...
14
Neuroimaging in PTSD
• Amygdala – hyperactivity, responsivity is
associated with PTSD symptom severity
• Frontal cortex...
15
Anterior cingulate cortex
• Interprets emotional stimuli and processes
responses
• Sympathetic ANS – “accelerator”
• Pa...
16
Anterior cingulate in PTSD
• Emotional Counting Stroop paradigm (pressing buttons)
• Blood oxygenation measured by fMRI...
17
“Speechless Terror”
• Suppression of Broca’s area during traumatic
reexperiencing (Rauch et al.)
• Construction of narr...
18
Failure of Extinction in PTSD
• Extinction: Decrease in conditioned response
due to nonreinforcement
• PTSD:
» Inabilit...
19
Extinction is an Active Cortical Process
• Cortical ablation studies – LeDoux
» Acquisition of conditioned fear respons...
20
AMYGDALA
Medial Prefrontal Cortex
Anterior Cingulate Cortex
Hippocampus
Thalamus
Sights
Sounds
Smells
Coordinated
Respo...
21
Salient Features of PTSD
• Hyperresponsiveness to stimuli that are
reminders of the trauma
? Amygdalar hyperactivity
• ...
22
PTSD: Treatment
23
24
Treatment Components
• Coping skills
• Medication
• Psychotherapy
• Alternative therapies
25
Institute of Medicine
“…scientific evidence on treatment
modalities for PTSD does not reach the
level of certainty that...
26
Treating people with PTSD is challenging
and rewarding. Success requires creativity,
flexibility, compassion, and clini...
27
Sri Lanka
28
“Dream Bubbles of Smoke and Blood” Ray-Paul Nielsen
29
30
When to Refer for Specialized
Psychiatric Care
• Medication failures or side effects
• Suicidal or homicidal ideation
•...
31
Basic Skills
• Relaxation, meditation, mindfulness training, coping skills
training, anger management, grounding, etc.
...
32
Approach to Medication Treatment
• Literature extremely limited, few controlled trials
• No specific agent for PTSD
• T...
33
Therapeutic Relationship
• Common barriers to alliance
• problems with authority, feelings of
powerlessness, fear of be...
34
Explore the Meaning of Medication
• Defective, weak, or damaged self
• Drugging or numbing – don’t want to listen to
co...
35
Symptomatic Treatment
• Inventory all symptoms
• Identify target symptoms for a given
medication
• Focus initial therap...
36
Psychoeducation and Control Issues
• Give patient (and family) information
» handouts, internet
» spark of recognition
...
37
Selective Serotonin Reuptake Inhibitors
(SSRIs)
• Sertraline (Zoloft), Paroxetine (Paxil),
Fluoxetine (Prozac), Citalop...
38
Other Antidepressants
• Venlafaxine (Effexor)
» dual mechanism of action
• Nefazodone (Serzone)
» lower sexual dysfunct...
39
Antidepressant Mechanism of Action
• We really don’t know
• Delayed mechanism of action postulated to
be via regulation...
40
Benzodiazepines: Anxiety and Sleep
• Alprazolam (Xanax) - short acting
• Clonazepam (Klonopin) - long acting
• Lorazepa...
41
Trazodone and Hydroxyzine
• Trazodone (Desyrel) - 50-200 mg for sleep,
25-100 for anxiety
• Hydroxyzine (Vistaril, Atar...
42
Newer Sleep Agents
• Zolpidem (Ambien)
• Zaleplon (Sonata)
• Eszopiclone (Lunesta)
• Different binding site on GABAA re...
43
Anticonvulsants
- Valproic Acid, Divalproex (Depakote)
- Carbamazepine (Tegretol)
- Lamotrigine (Lamictal)
- Anger, moo...
44
Antipsychotics
• Risperidone (Risperdal), Olanzapine (Zyprexa),
Ziprasidone (Geodon), Quetiapine (Seroquel),
Aripiprazo...
45
Prazosin for Nightmares
• Alpha-1 adrenergic antagonist commonly used to
treat high blood pressure and enlarged prostat...
46
Approach to Psychotherapy
• Three stages: safety, remembering, reconnection
• Education about trauma and PTSD
• Normali...
47
Effective Therapies
• Exposure Therapy: Desensitization
• Cognitive Therapy: Dysfunctional beliefs and
behaviors
48
PFC -L PFC -M
thought extinction
AMYGDALADRUGS
side
effects
AMYGDALA
Therapy for Fear/Anxiety Problems
(After LeDoux)
49
VA Therapeutic Menu
• Cognitive Behavioral Skills (CBT)
• Prolonged Exposure (PE)
• Cognitive Processing Therapy (CPT)
...
50
Alternative therapies
• Art therapy
• Somatic therapies/bodywork
• Acupuncture
• Yoga
• Tai Chi
• Religious/spiritual p...
51
Traditional Sweat Lodge
52
53
D-Cycloserine
• Extinction is an active cortical process – requires
learning – Joseph LeDoux
• NMDA receptor mediated c...
54
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PPT - Prazosin Reduces Nightmares and Other PTSD Symptomns in ...

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  • PTSD is a brain injury. It is a war wound no less than is a shrapnel wound.
  • I liked this photo -- it's one of the Israeli volunteers in Sri Lanka playing with some of the young tsunami victims.
    The volunteers are part of a team of trauma specialists who were dispatched to Sri Lanka to help the children cope with the huge losses they have experienced. They get the children to act like monsters, making faces and being very loud and aggressive and in that way allow the children to express all the anger and fear that they're too traumatized to be able to express naturally.
    They watch the children playing and can identify those that have the the most deep-rooted traumas from their inability to play act. ITV news featured them in a follow-up news programme last week. It was incredible, they identified four children that weren't able to connect with being monsters and couldn't yell and scream. They took them to a quiet place and discovered that each child had a particularly harrowing story and each of them had lost mutiple family members, including one or both parents.
    It is apparently a technique that was pioneered in Israel from experience with the bus bombings. There are some things that are just so horrible that children don't have the words to express what they have seen and how bad they feel and they just shut down. Their experiences are so far out of the realm of their lives and their understanding that they completely block it out. By making them scream and shout at something that they can relate to you "unlock" the scream that they need to scream and allow them to emote.
    (Many thanks to my dear friend in Fiona in Great Britain who clued me in to exactly what the photos were showing. Originally, I had just put up the photo -- the description of the program is hers from the comments.)
  • Transcript of "PPT - Prazosin Reduces Nightmares and Other PTSD Symptomns in ..."

    1. 1. 1 PTSD: Neurobiology
    2. 2. 2 Neurophysiologic Alterations in PTSD • Stress hormone systems - adrenal gland » Sympatho-adrenomedullary » Hypothlamic-pituitary-adrenal • Neurotransmitter systems • Thyroid • Immune system • Amygdala hyperactivity – fear and anger • Hippocampal volume loss – memory deficits • Anterior cingulate – “emotional clutch”
    3. 3. 3 Adrenergic Alterations • Exaggerated increases in cardiovascular responses to trauma-specific stimuli • Increased catecholamines in urine, plasma, CSF • Decreased platelet α-2 receptors • Yohimbine induced panic attacks
    4. 4. 4 HPA Axis Alterations PTSD Major Depression Cortisol levels Low High Glucocorticoid receptors Increased Decreased Dexamethasone Hypersuppression Nonsuppression Negative feedback Stronger Weaker CSF CRF levels Increased Increased
    5. 5. Hypothalamus CRF Posterior Pituitary Anterior Pituitary ACTH Adrenal Kidney Norepinephrine ↑ Cortisol ↓ PTSD
    6. 6. 6 Stress Hormone Systems •Norepinephrine – “revving up” hormone •Cortisol – “quieting down” hormone •Both hormones are released in response to stress. They are normally in balance.
    7. 7. 7 LeDoux, Scientific American, 1994
    8. 8. 8 Hiker and Snake • Immediate response - Fight or flight - Quick and dirty • Delayed response - Recognition, planning - Slow and accurate
    9. 9. 9 SENSORY CORTEX SENSORY THALAMUS AMYGDALA EMOTIONAL STIMULUS EMOTIONAL RESPONSES “High Road” “Low Road”
    10. 10. 10 Why do I get so angry? What’s wrong with my memory? • Amygdala » “Reptile brain, dinosaur brain” » Emotional response » Fear, anger, fight or flight • Frontal lobe » “Executive function” » Cognitive response » Working memory, attention, carrying out tasks
    11. 11. 11
    12. 12. 12
    13. 13. 13 “Battlemind” • In a dangerous situation you don’t want to sit around and think. You want to act immediately using your amygdala and bypassing your frontal lobe. • In PTSD the brain acts like you are in a dangerous situation all the time. The amygdala is hyperactive and the frontal lobe functions poorly. • Anger and poor concentration are related. They are both part of hyperarousal.
    14. 14. 14 Neuroimaging in PTSD • Amygdala – hyperactivity, responsivity is associated with PTSD symptom severity • Frontal cortex – volume loss, responsivity is inversely associated with PTSD symptom severity • Hippocampus – volume loss, decreased neuronal and functional integrity
    15. 15. 15 Anterior cingulate cortex • Interprets emotional stimuli and processes responses • Sympathetic ANS – “accelerator” • Parasympathetic ANS – “brakes” • Anterior cingulate – “clutch”
    16. 16. 16 Anterior cingulate in PTSD • Emotional Counting Stroop paradigm (pressing buttons) • Blood oxygenation measured by fMRI • Recruitment of anterior cingulate increased when counting combat-related words only in controls and not in PTSD subjects - Shin et al, Biol Psychiatry 2001
    17. 17. 17 “Speechless Terror” • Suppression of Broca’s area during traumatic reexperiencing (Rauch et al.) • Construction of narrative promotes reencoding of traumatic memories • Subcortical memories - somatosensory • Cortical memories – verbal, symbolic
    18. 18. 18 Failure of Extinction in PTSD • Extinction: Decrease in conditioned response due to nonreinforcement • PTSD: » Inability to extinguish conditioned fear responses » Inability to distinguish between dangerous and safe situations
    19. 19. 19 Extinction is an Active Cortical Process • Cortical ablation studies – LeDoux » Acquisition of conditioned fear responses requires only subcortical structures » Cortical ablation greatly prolongs or prevents extinction of fear responses • “Indelibility of subcortical emotional memories” • Extinction requires learning
    20. 20. 20 AMYGDALA Medial Prefrontal Cortex Anterior Cingulate Cortex Hippocampus Thalamus Sights Sounds Smells Coordinated Response + + + _ _ Coordination of Threat Response
    21. 21. 21 Salient Features of PTSD • Hyperresponsiveness to stimuli that are reminders of the trauma ? Amygdalar hyperactivity • Overgeneralization of stimuli ? Hippocampal dysfunction • Anger dyscontrol, Failure of extinction ? Medial prefrontal cortex dysfunction
    22. 22. 22 PTSD: Treatment
    23. 23. 23
    24. 24. 24 Treatment Components • Coping skills • Medication • Psychotherapy • Alternative therapies
    25. 25. 25 Institute of Medicine “…scientific evidence on treatment modalities for PTSD does not reach the level of certainty that would be desired for such a common and serious condition among veterans… additional high quality research is essential for every treatment modality.”
    26. 26. 26 Treating people with PTSD is challenging and rewarding. Success requires creativity, flexibility, compassion, and clinical skill. Be aware of secondary traumatization.
    27. 27. 27 Sri Lanka
    28. 28. 28 “Dream Bubbles of Smoke and Blood” Ray-Paul Nielsen
    29. 29. 29
    30. 30. 30 When to Refer for Specialized Psychiatric Care • Medication failures or side effects • Suicidal or homicidal ideation • Comorbid psychiatric problems including substance abuse • Other life stressors, limited social support
    31. 31. 31 Basic Skills • Relaxation, meditation, mindfulness training, coping skills training, anger management, grounding, etc. » Tolerate negative emotion » Use social support » Calm/soothe self » Moderate self-loathing » Control destructive impulses (self-harm, violence, substance abuse) » Articulate feelings » Maintain hope
    32. 32. 32 Approach to Medication Treatment • Literature extremely limited, few controlled trials • No specific agent for PTSD • Treat prominent symptoms • Treat comorbidity
    33. 33. 33 Therapeutic Relationship • Common barriers to alliance • problems with authority, feelings of powerlessness, fear of being exploited • intense mistrust and/or isolation • Support concurrent psychotherapy • Initial pharmacotherapy may allow later psychotherapy and vice versa
    34. 34. 34 Explore the Meaning of Medication • Defective, weak, or damaged self • Drugging or numbing – don’t want to listen to complaints • Failure in psychotherapy • Unrealistic wish for med to erase traumatic event > Assess fears and fantasies as you monitor benefits and side effects
    35. 35. 35 Symptomatic Treatment • Inventory all symptoms • Identify target symptoms for a given medication • Focus initial therapy on one or two most distressing symptoms • Often significant resistance to improvement, e.g. hypervigilance
    36. 36. 36 Psychoeducation and Control Issues • Give patient (and family) information » handouts, internet » spark of recognition • Give the patient control » titration decisions » meds like trazodone, hydroxyzine useful in this regard
    37. 37. 37 Selective Serotonin Reuptake Inhibitors (SSRIs) • Sertraline (Zoloft), Paroxetine (Paxil), Fluoxetine (Prozac), Citalopram (Celexa), Escitalopram (Lexapro) • All 3 symptom clusters may respond • Sexual dysfunction • Arousal - “Jitteriness” • Nausea, diarrhea, headache, insomnia
    38. 38. 38 Other Antidepressants • Venlafaxine (Effexor) » dual mechanism of action • Nefazodone (Serzone) » lower sexual dysfunction, liver toxicity? • Mirtazapine (Remeron) » sedation, weight gain • Buproprion (Wellbutrin) » activation, increased energy, smoking cessation • Duloxetine (Cymbalta) » dual action, chronic pain? • Tricyclic Antidepressants: Amitriptyline, Nortriptyline, Desipramine, Imipramine » chronic pain, many side effects
    39. 39. 39 Antidepressant Mechanism of Action • We really don’t know • Delayed mechanism of action postulated to be via regulation of gene expression » Genes for neurotransmitter receptors » Genes for neurotrophic factors • Often confusing for patient » Assessment of family/friends may be important
    40. 40. 40 Benzodiazepines: Anxiety and Sleep • Alprazolam (Xanax) - short acting • Clonazepam (Klonopin) - long acting • Lorazepam (Ativan) • Diazepam (Valium) • Temazepam (Restoril) - sleep • Chlordiazepoxide (Librium) – alcohol withdrawal • GABAA receptor binding and potentiation • Caution - high addiction potential
    41. 41. 41 Trazodone and Hydroxyzine • Trazodone (Desyrel) - 50-200 mg for sleep, 25-100 for anxiety • Hydroxyzine (Vistaril, Atarax) - 25-100 mg for sleep and anxiety, also Diphenhydramine (Benadryl)
    42. 42. 42 Newer Sleep Agents • Zolpidem (Ambien) • Zaleplon (Sonata) • Eszopiclone (Lunesta) • Different binding site on GABAA receptor • Less addictive, expensive
    43. 43. 43 Anticonvulsants - Valproic Acid, Divalproex (Depakote) - Carbamazepine (Tegretol) - Lamotrigine (Lamictal) - Anger, moodswings, violent behavior - Comorbid bipolar disorder - Antidepressant augmentation
    44. 44. 44 Antipsychotics • Risperidone (Risperdal), Olanzapine (Zyprexa), Ziprasidone (Geodon), Quetiapine (Seroquel), Aripiprazole (Abilify) • “Psychotic” symptoms including prominent hallucinations, paranoia • Affective instability (Borderline PD) • Antidepressant augmentation
    45. 45. 45 Prazosin for Nightmares • Alpha-1 adrenergic antagonist commonly used to treat high blood pressure and enlarged prostate • Lipid soluble – crosses blood-brain barrier • Slow titration • Orthostatic dizziness, including first dose effect • Headache, nausea, congestion, tachycardia
    46. 46. 46 Approach to Psychotherapy • Three stages: safety, remembering, reconnection • Education about trauma and PTSD • Normalization and validation • Relieve irrational guilt • Determine ability to tolerate memories without decompensation or intolerable self-loathing • Group therapy • Evidence-based therapy
    47. 47. 47 Effective Therapies • Exposure Therapy: Desensitization • Cognitive Therapy: Dysfunctional beliefs and behaviors
    48. 48. 48 PFC -L PFC -M thought extinction AMYGDALADRUGS side effects AMYGDALA Therapy for Fear/Anxiety Problems (After LeDoux)
    49. 49. 49 VA Therapeutic Menu • Cognitive Behavioral Skills (CBT) • Prolonged Exposure (PE) • Cognitive Processing Therapy (CPT) • Acceptance and Commitment Therapy (ACT) • Eye Movement Desensitization and Reprocessing (EMDR) • Addictions Treatment • Behavioral Activation • Interpersonal Skills • Imagery Rehearsal Therapy • Sleep Improvement • Mindfulness • Wellness (Diet, Exercise, Smoking Cessation) • Work Readiness • Life Transitions
    50. 50. 50 Alternative therapies • Art therapy • Somatic therapies/bodywork • Acupuncture • Yoga • Tai Chi • Religious/spiritual practices • Virtual reality
    51. 51. 51 Traditional Sweat Lodge
    52. 52. 52
    53. 53. 53 D-Cycloserine • Extinction is an active cortical process – requires learning – Joseph LeDoux • NMDA receptor mediated calcium influx underlies learning and memory • NMDA receptor agonist at the glycine site, potentiates neurotransmission, facilitates extinction of conditioned fear • Increases effectiveness of treatment when paired with exposure therapy.
    54. 54. 54
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