PTSD: Neurobiology Neurophysiologic Alterations in PTSD

PTSD: Neurobiology

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”

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

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

Hypothalamus CRF Posterior Pituitary Anterior Pituitary ACTH Adrenal Kidney Norepinephrine  Cortisol  PTSD

Stress Hormone Systems
Norepinephrine – “revving up” hormone
Cortisol – “quieting down” hormone
Both hormones are released in response to stress. They are normally in balance.

LeDoux, Scientific American, 1994

Hiker and Snake
Immediate response
- Fight or flight
- Quick and dirty
Delayed response
- Recognition, planning
- Slow and accurate

SENSORY CORTEX SENSORY THALAMUS AMYGDALA EMOTIONAL STIMULUS EMOTIONAL RESPONSES “ High Road” “ Low Road”

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

“ 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.

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

Anterior cingulate cortex
Interprets emotional stimuli and processes responses
Sympathetic ANS – “accelerator”
Parasympathetic ANS – “brakes”
Anterior cingulate – “clutch”

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

“ 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

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

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”

AMYGDALA Medial Prefrontal Cortex Anterior Cingulate Cortex Hippocampus Thalamus Sights Sounds Smells Coordinated Response + + + _ _ Coordination of Threat Response

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

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.”

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

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

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

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

Husband Wife Functional MRI Responses to Traumatic Imagery

PTSD: Treatment

Treatment Components
Coping skills
Medication
Psychotherapy
Alternative therapies

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.”

Treating people with PTSD is challenging and rewarding. Success requires creativity, flexibility, compassion, and clinical skill.
Be aware of secondary traumatization.

Sri Lanka

“ Dream Bubbles of Smoke and Blood” Ray-Paul Nielsen

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

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

Approach to Medication Treatment
 Literature extremely limited, few controlled trials
 No specific agent for PTSD
 Treat prominent symptoms
 Treat comorbidity

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

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

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

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

SSRIs
Sertraline (Zoloft), Paroxetine (Paxil), Fluoxetine (Prozac), Citalopram (Celexa)
All 3 symptom clusters may respond
Sexual dysfunction
Arousal - “Jitteriness”
Nausea, diarrhea, headache, insomnia

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

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

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)

Newer Sleep Agents
Zolpidem (Ambien)
Zaleplon (Sonata)
Eszopiclone (Lunesta)
Different binding site on GABA A receptor
Less addictive, expensive

Anticonvulsants
Valproic Acid, Divalproex (Depakote)
Carbamazepine (Tegretol)
Lamotrigine (Lamictal)
Anger, moodswings, violent behavior
Comorbid bipolar disorder
Antidepressant augmentation

Antipsychotics
Risperidone (Risperdal), Olanzapine (Zyprexa), Ziprasidone (Geodon), Quetiapine (Seroquel), Aripiprazole (Abilify)
“ Psychotic” symptoms including prominent hallucinations, paranoia
Affective instability (Borderline PD)
Antidepressant augmentation

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

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

Effective Therapies
Exposure Therapy: Desensitization
Cognitive Therapy: Dysfunctional beliefs and behaviors

thought extinction AMYGDALA DRUGS side effects AMYGDALA Therapy for Fear/Anxiety Problems (After LeDoux)

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

Alternative therapies
Art therapy
Somatic therapies/bodywork
Acupuncture
Yoga
Tai Chi
Religious/spiritual practices
Virtual reality

Traditional Sweat Lodge

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

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PTSD: Neurobiology Neurophysiologic Alterations in PTSD

by dominic54 on Oct 28, 2010

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PTSD: Neurobiology Neurophysiologic Alterations in PTSD — Presentation Transcript