WHEN SOCIAL PSYCHOLOGY AND WHEN SOCIAL PSYCHOLOGY AND NEUROSCIENCE RESEARCH NEUROSCIENCE RESEARCH

MERGEMERGEThe case of PTSDThe case of PTSD

Julius LandwirthJulius Landwirth

Yale Interdisciplinary Center for Yale Interdisciplinary Center for BioethicsBioethics

Emergence of PTSDEmergence of PTSD

Wartime problem : Civil war-KoreaWartime problem : Civil war-Korea Shell shockShell shock War neurosisWar neurosis Battle fatigueBattle fatigue

Symptoms thought to disappear after Symptoms thought to disappear after dischargedischarge

Vietnam: Vietnam: Chronic mental health diseaseChronic mental health disease

Diagnostic CriteriaDiagnostic Criteria

DSM-3 , 1980 (“Official disease”)DSM-3 , 1980 (“Official disease”)

Traumatic experience (not just war)Traumatic experience (not just war)

Re-experience (nightmares,flashbacks)Re-experience (nightmares,flashbacks)

Avoidance (of topic,of people)Avoidance (of topic,of people)

Hyper-arousal (startle, poor Hyper-arousal (startle, poor sleep,memory,concentration)sleep,memory,concentration)

Research impact:Research impact:

International Society for Traumatic Stress International Society for Traumatic Stress StudiesStudies

Journal of Traumatic Stress Journal of Traumatic Stress

Current criteria Current criteria DSM-4-TR (2000)DSM-4-TR (2000)

Intrusive recollection (dreams, flashes)Intrusive recollection (dreams, flashes)Avoidance/numbing (memory, Avoidance/numbing (memory,

concentration, disinterest,detachment)concentration, disinterest,detachment) Hyper-arousal (sleep, outbursts, startle, Hyper-arousal (sleep, outbursts, startle,

hyper-vigilance)hyper-vigilance) Duration ( > 1 month)Duration ( > 1 month) Functional significanceFunctional significance

““Conceptual bracket creep” ?Conceptual bracket creep” ?

Criterion A: StressorCriterion A: Stressor

““ The person has experienced, witnessed, or been The person has experienced, witnessed, or been confronted with an event or events that involve actual or confronted with an event or events that involve actual or threatened death or serious injury, or a threat to the threatened death or serious injury, or a threat to the physical integrity of oneself or others”physical integrity of oneself or others”

Disease Disease vsvs medicalization of normal distress reactions ? medicalization of normal distress reactions ?

Epidemiology/public healthEpidemiology/public health

Combat veteransCombat veterans ( Iraq, Afghanistan): ( Iraq, Afghanistan):Health surveys of 88,235 active and reserve Health surveys of 88,235 active and reserve soldiers, upon deployment and 3-6 months later.soldiers, upon deployment and 3-6 months later.

PTSD symptoms increased PTSD symptoms increased 11.8-16.7% in active group11.8-16.7% in active group

12.7-24.5% in reserve group12.7-24.5% in reserve group

Milliken CS, et al. Milliken CS, et al. JAMA 2007 ;298:2141-2148JAMA 2007 ;298:2141-2148

************************VA cost for PTSD: $4.3 billion in 2004VA cost for PTSD: $4.3 billion in 2004

Epidemiology/public healthEpidemiology/public health

General Public General Public - About 7% may develop PTSD during - About 7% may develop PTSD during

lifetimelifetime - 20 years of active symptoms- 20 years of active symptoms - 1 day/week work impairment- 1 day/week work impairment - 19 % suicide risk- 19 % suicide risk - $3 billion annual productivity loss- $3 billion annual productivity loss Cited in Kolber AM, Vanderbilt Law Review 2006;59:1561-1625Cited in Kolber AM, Vanderbilt Law Review 2006;59:1561-1625

Emotionally charged memoriesEmotionally charged memories

Hippocampus, amygdalaHippocampus, amygdala

Consolidation, re-consolidationConsolidation, re-consolidation

Hypothalamic-pituitary-adrenal axisHypothalamic-pituitary-adrenal axis

“ “ Each time you retrieve a memory it must Each time you retrieve a memory it must be restored. When you activate a memory be restored. When you activate a memory in the presence of a drug that prevents the in the presence of a drug that prevents the storage of the memory, the next day the storage of the memory, the next day the memory is not as accessible”memory is not as accessible”

Joseph LeDoux, NYUJoseph LeDoux, NYU

neuroscientistneuroscientist

The Quest to ForgetThe Quest to Forget

R.A. Henig, NY Times, April 4, 2004R.A. Henig, NY Times, April 4, 2004

A Pill to fade traumatic memories ? Doctors A Pill to fade traumatic memories ? Doctors are working on itare working on it

M. Marchione, Assoc Press, Jan 14, 2006M. Marchione, Assoc Press, Jan 14, 2006

Research on humansResearch on humans

37 people received either drug (propanolol)37 people received either drug (propanolol)

or placebo prior to stimulus exposureor placebo prior to stimulus exposure

Slides telling 2 stories:Slides telling 2 stories:

1) Boy on way to hospital to visit father1) Boy on way to hospital to visit father

sees car accident. Sees ER drillsees car accident. Sees ER drill

2) Boy injured, ER works on shattered legs2) Boy injured, ER works on shattered legs

ResultsResults

1 week later, subjects asked to recall details, 1 week later, subjects asked to recall details, also measured heart rates also measured heart rates

In story # 1 (non-arousal), no differenceIn story # 1 (non-arousal), no difference

In story #2 (arousal), those on placebo In story #2 (arousal), those on placebo remembered gory details, faster heart rateremembered gory details, faster heart rate

(facts of stories not changed)(facts of stories not changed)

Ethical issuesEthical issues

Treating 100% within 6 hours to prevent Treating 100% within 6 hours to prevent 30%30%

Presidents Commission on Bioethics (2003)Presidents Commission on Bioethics (2003)- may interfere with coming to terms with - may interfere with coming to terms with traumatrauma

- tampering with identity; false sense of - tampering with identity; false sense of happinesshappiness

- demeans genuinness of human life - demeans genuinness of human life experienceexperience

Ethical issuesEthical issues

- forgetting events we are obliged to - forgetting events we are obliged to rememberremember

- inure us against pain of others- inure us against pain of others

Legal issuesLegal issues

- Tampering with socially valuable Tampering with socially valuable information ( evidence)information ( evidence)

- Mitigation of emotional injury damagesMitigation of emotional injury damages

Research ethics concernsResearch ethics concerns

- VulnerabilityVulnerability- Informed consentInformed consent- Psychological challenge studyPsychological challenge study

- How to justify enrolling participants - How to justify enrolling participants into study in which potentially harmful into study in which potentially harmful response is intentionally inducedresponse is intentionally induced

APA Task Force on Research APA Task Force on Research Ethics ( 2006)Ethics ( 2006)

“ “ Research strategies that may prolong or Research strategies that may prolong or exacerbate symptoms can be justified when exacerbate symptoms can be justified when practicable alternative research strategies have practicable alternative research strategies have been carefully considered and found been carefully considered and found scientifically inadequate and when clear plans scientifically inadequate and when clear plans are developed to minimize negative effects and are developed to minimize negative effects and to ensure the safety of research participants “to ensure the safety of research participants “

Which means…Which means…

- Prelim dataPrelim data- Screening for susceptabilityScreening for susceptability- Potential for minor injuryPotential for minor injury- Potential for transient injuryPotential for transient injury- Availability of treatmentAvailability of treatment- Withdrawal from studyWithdrawal from study- Monitor for fluctuating cognitionMonitor for fluctuating cognition- etc- etc

Questions to ponderQuestions to ponder

What ethical issues might arise from the What ethical issues might arise from the availability of drugs that can blunt availability of drugs that can blunt traumatic memories ?traumatic memories ?

What ethical issues might arise in the What ethical issues might arise in the conduct of research testing such drugs on conduct of research testing such drugs on human subjects ?human subjects ?

The EndThe End

ThanksThanks

Case studyCase study

The use of Propanolol to block memory The use of Propanolol to block memory

reconsolidation in PTSD reconsolidation in PTSD

Research planResearch plan

Participant recruitment flyer:Participant recruitment flyer:

“ “ Do you have upsetting memories from combat in Do you have upsetting memories from combat in Iraq or Afghanistan ?Iraq or Afghanistan ?

Male veterans from Operations OIF/OEF are Male veterans from Operations OIF/OEF are needed for research using one day’s dose of a needed for research using one day’s dose of a beta-block medication (propanolol) to see if it beta-block medication (propanolol) to see if it has an effect on upsetting combat memories.has an effect on upsetting combat memories.

Payment up to $400 for a total of 4 visits”Payment up to $400 for a total of 4 visits”

Study designStudy design

30 participants randomly assigned to 3 grps30 participants randomly assigned to 3 grps

1) Propanolol for traumatic memory;placebo 1) Propanolol for traumatic memory;placebo for neutralfor neutral

2) Placebo for traumatic memory;propanolol 2) Placebo for traumatic memory;propanolol for neutral memoryfor neutral memory

3) Placebo for traumatic and neutral memory3) Placebo for traumatic and neutral memory

Research designResearch design

Visit # 1:Visit # 1:

-Consent form-Consent form

-Screen for incl/excl (urine, cardiac, history, physical)-Screen for incl/excl (urine, cardiac, history, physical)

-Standard questionnaires to confirm PTSD and severity –-Standard questionnaires to confirm PTSD and severity –Audio-taped interviews (80 min) to ascertain neutral Audio-taped interviews (80 min) to ascertain neutral (daily life) and traumatic memory cues(daily life) and traumatic memory cues

Research designResearch design

Visit #2 ( first memory session):Visit #2 ( first memory session):

-Repeat drug screen-Repeat drug screen -Attach psychophysio monitors (hr,skin conduct,facial -Attach psychophysio monitors (hr,skin conduct,facial

emg), baseline recordingsemg), baseline recordings -30-sec neutral tape, 30-sec recall-30-sec neutral tape, 30-sec recall -40 mg Propanolol immediately, 60 mg 2 hrs later-40 mg Propanolol immediately, 60 mg 2 hrs later or placebo depending on group assignmentor placebo depending on group assignment

Research designResearch design

Visit # 3 (second memory session):Visit # 3 (second memory session):

-Same procedure using traumatic memory -Same procedure using traumatic memory cuescues

-Propanolol or placebo per group -Propanolol or placebo per group assignmentassignment

Research designResearch design

Visit # 4 ( 2 week follow-up)Visit # 4 ( 2 week follow-up)

-Repeat drug screen-Repeat drug screen

-All groups hear their traumatic memory -All groups hear their traumatic memory cue againcue again

-Standard questionnaire to assess change -Standard questionnaire to assess change in PTSD symptomsin PTSD symptoms

Respect for personsRespect for persons

social valuesocial value

scientific merit scientific merit

informed consent (ongoing)informed consent (ongoing)

respect for participantsrespect for participants

BeneficenceBeneficence

Favorable risk-benefit ratioFavorable risk-benefit ratio

Minimizing risk of harmMinimizing risk of harm

Independent reviewIndependent review

Risk/benefit Risk/benefit

“ “ Participation in this study exposes the participants to Participation in this study exposes the participants to greater than minimal risk….participants will contribute greater than minimal risk….participants will contribute

toward further understanding of the biological toward further understanding of the biological mechanisms underlying PTSD and its treatments….may mechanisms underlying PTSD and its treatments….may benefit the individual…great benefit to society…risks benefit the individual…great benefit to society…risks posed by this study are reasonable when weighed posed by this study are reasonable when weighed against these potential contributions…”against these potential contributions…”

Minimizing riskMinimizing risk

“…“…risk associated with participation…will be risk associated with participation…will be minimized by close monitoring…the minimized by close monitoring…the apprehension some individuals may feel apprehension some individuals may feel during the memory reactivation test is during the memory reactivation test is slight and short-lived. Participants will be slight and short-lived. Participants will be reminded that they can stop the study at reminded that they can stop the study at any time’any time’

JusticeJustice

Fair subject selectionFair subject selection

(military personnel ?)(military personnel ?)