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PTSD: Neurobiology Neurophysiologic Alterations in PTSD






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  • Very well documented. Congrats!!
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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.)

PTSD: Neurobiology Neurophysiologic Alterations in PTSD Presentation Transcript

  • 1. PTSD: Neurobiology
  • 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. Adrenergic Alterations
    • Exaggerated increases in cardiovascular responses to trauma-specific stimuli
    • Increased catecholamines in urine, plasma, CSF
    • Decreased platelet  -2 receptors
    • Yohimbine induced panic attacks
  • 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. 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 released in response to stress. They are normally in balance.
  • 7. LeDoux, Scientific American, 1994
  • 8. Hiker and Snake
    • Immediate response
      • - Fight or flight
      • - Quick and dirty
    • Delayed response
      • - Recognition, planning
      • - Slow and accurate
  • 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.  
  • 12.  
  • 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. 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. Anterior cingulate cortex
    • Interprets emotional stimuli and processes responses
    • Sympathetic ANS – “accelerator”
    • Parasympathetic ANS – “brakes”
    • Anterior cingulate – “clutch”
  • 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. “ 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. 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. 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”
  • 20. AMYGDALA Medial Prefrontal Cortex Anterior Cingulate Cortex Hippocampus Thalamus Sights Sounds Smells Coordinated Response + + + _ _ Coordination of Threat Response
  • 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. Individual Differences in a Husband and Wife Who Developed PTSD After a Motor Vehicle Accident: A Functional MRI Case Study Lanius RA, Hopper JW, Menon RS. Am J Psychiatry 160:4, April 2003 667-669 “ Both subjects were trapped in their car for several minutes, during which they witnessed a child burn to death and feared that they too would die.”
  • 23. Trauma Response - Husband
    • Extremely aroused, actively involved in rescue – broke windshield
    • Nightmares and flashbacks started next day, often felt as if accident were recurring
    • Psychological and physiological arousal when thinking or talking about accident
    • Severely impaired, unable to function at work
  • 24. Trauma Response - Wife
    • Felt “in shock, frozen”
    • Nightmares and flashbacks started next day, often felt as if accident were recurring
    • Reexperiencing involved feeling numb and frozen
    • Severely impaired, unable to function at work
    • H/O early parental loss, postpartum depression, mild panic disorder
  • 25. Script-Driven Imagery - Husband
    • Intense anxiety, arousal, escape-focused cognitions
    • Increased heart rate
    • Increased activation of multiple regions including anterior frontal, anterior cingulate, thalamus, amygdala
    • Exposure therapy x 6 mos - No PTSD
  • 26. Script-Driven Imagery - Wife
    • Felt extremely “numb” and “frozen”
    • No increase in heart rate
    • Increased activation only in occipital region
    • Exposure therapy x 6 mos - Still had PTSD
  • 27. Husband Wife Functional MRI Responses to Traumatic Imagery
  • 28. PTSD: Treatment
  • 29.  
  • 30. Treatment Components
    • Coping skills
    • Medication
    • Psychotherapy
    • Alternative therapies
  • 31. 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.”
  • 32.
    • Treating people with PTSD is challenging and rewarding. Success requires creativity, flexibility, compassion, and clinical skill.
    • Be aware of secondary traumatization.
  • 33. Sri Lanka
  • 34. “ Dream Bubbles of Smoke and Blood” Ray-Paul Nielsen
  • 35.  
  • 36. 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
  • 37. 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
  • 38. Approach to Medication Treatment
    •  Literature extremely limited, few controlled trials
    •  No specific agent for PTSD
    •  Treat prominent symptoms
    •  Treat comorbidity
  • 39. 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
  • 40. 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
  • 41. 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
  • 42. 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
  • 43. SSRIs
    • Sertraline (Zoloft), Paroxetine (Paxil), Fluoxetine (Prozac), Citalopram (Celexa)
    • All 3 symptom clusters may respond
    • Sexual dysfunction
    • Arousal - “Jitteriness”
    • Nausea, diarrhea, headache, insomnia
  • 44. Other Antidepressants
    • Nefazodone (Serzone)
      • lower sexual dysfunction, liver toxicity?
    • Venlafaxine (Effexor)
      • dual mechanism of action
    • Mirtazapine (Remeron)
      • sedation, weight gain
    • Buproprion (Wellbutrin)
      • activation, increased energy, smoking cessation
    • Tricyclic Antidepressants: Amitriptyline, Nortriptyline, Desipramine, Imipramine
      • chronic pain, many side effects
  • 45. Benzodiazepines: Anxiety and Sleep
    • Alprazolam (Xanax) - short acting
    • Clonazepam (Klonopin) - long acting
    • Lorazepam (Ativan)
    • Diazepam (Valium)
    • Temazepam (Restoril) - sleep
    • Chlordiazepoxide (Librium) – alcohol withdrawal
    • GABA A receptor binding and potentiation
    • Caution - high addiction potential
  • 46. 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)
  • 47. Newer Sleep Agents
    • Zolpidem (Ambien)
    • Zaleplon (Sonata)
    • Eszopiclone (Lunesta)
    • Different binding site on GABA A receptor
    • Less addictive, expensive
  • 48. Anticonvulsants
      • Valproic Acid, Divalproex (Depakote)
      • Carbamazepine (Tegretol)
      • Lamotrigine (Lamictal)
      • Anger, moodswings, violent behavior
      • Comorbid bipolar disorder
      • Antidepressant augmentation
  • 49. Antipsychotics
    • Risperidone (Risperdal), Olanzapine (Zyprexa), Ziprasidone (Geodon), Quetiapine (Seroquel), Aripiprazole (Abilify)
    • “ Psychotic” symptoms including prominent hallucinations, paranoia
    • Affective instability (Borderline PD)
    • Antidepressant augmentation
  • 50. 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
  • 51. 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
  • 52. Effective Therapies
    • Exposure Therapy: Desensitization
    • Cognitive Therapy: Dysfunctional beliefs and behaviors
  • 53. thought extinction AMYGDALA DRUGS side effects AMYGDALA Therapy for Fear/Anxiety Problems (After LeDoux)
  • 54. 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
  • 55. Alternative therapies
    • Art therapy
    • Somatic therapies/bodywork
    • Acupuncture
    • Yoga
    • Tai Chi
    • Religious/spiritual practices
    • Virtual reality
  • 56. Traditional Sweat Lodge
  • 57.  
  • 58. 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.
    • Drug development company – Mike Davis
  • 59.