PTSD - ukpts

PTSD - ukpts

Introduction to TraumaticStress (part one)An overview of traumatic events,reactions, conceptualisations &neurobiologyAlastair HullConsultant Psychiatrist in PsychotherapyUnited Kingdom Psychological Trauma Society, Regional Conference, City Hall, Cardiff, 2012

Importance of Trauma• patients with chronic depression– a history of early life trauma predicts the need forpsychotherapy as an adjunct to pharmacotherapy(CBASP: Nemeroff et al, 2003)• high percentage of patients with bipolar disorderhave a history of childhood deprivation or abuse(50%; Garno et al, 2005)• high rates of trauma exposure in the populationand in psychiatric inpatients• non-recording of significant trauma common(Mueser et al, 1998; Hull et al, 2010)

Importance of Trauma• Trauma exposure is associated with effects uponphysical health– Health care utilisation– Infections, pain disorders, hypertension, diabetes,asthma, allergies• Post-traumatic Stress Disorder (PTSD) isassociated with effects upon physical health– Excess all-cause mortality– Chronic diseases such as cardiovascular, digestive(including liver disease), musculoskeletal, endocrine andrespiratory– Stands up even when control for other factors (includingalcohol and drugs)

Traumatic eventsINDIVIDUALS EXPOSED• Intentional– assault– robbery– rape• Unintentional(i.e., accidental*)– motor vehicle accident– industrial accident*with apologies to the BMJ

Background about TraumaWhat we think we know about traumatic events:• Easy to define what = traumatic event (DSM & ICD)• There are differences between technological and naturaltrauma (for example, disasters)• Traumatic events are equal opportunity events• Some individuals more at risk of adverse psychologicalreactions• Early intervention is helpful• The Media are intrusive & unhelpful

Media and the community• Overseas disasters “one of them” until realise one of our citizensaffected, becomes “one of us” (for example, Tsunami)• Piper Alpha– “us” stories in local papers, TV stations in Scotland– despite many men being from England• Chilean miners– BBC reported by other media as using up a large proportion of budget on 1disaster- accuracy of report?• Media loves mythologies– creation of heroes– Around causality and victimisation• (e.g., 3 Mile Island; The ChinaSyndrome)

Positive experience of trauma• 50 years after surviving the Bataan DeathMarch & 42 months internment in a POWcamp “wouldn’t repeat for a million dollars”but, recalled as the most enriching &ennobling experience of his life• approximately 2/3rds of survivors of PiperAlpha disaster described positive sequelae• examples of cognitive reframing

Definition of a disaster“…a severe disruption, ecological and psychosocial,which greatly exceeds the coping capacity of theaffected community” (World Health Organisation, 1992)

Media and the community• BUT, media not moving on to the next eventcauses problems– new disaster not covered- becomes a hidden disaster– for example, Tennessee floods happened at same timeas another disaster and terrorist attack– less funds raised for relief– people felt marginalised• What message is given to individual trauma survivor bythe excessive interest in disaster survivor?– the psychological effects are same/similar

A Piper Alpha myth debunked- Working offshore• worked offshore again after the disaster 33%• did not go back offshore because of disaster 47%• believe employers not keen to employ to 14%work offshore again• able to adjust to working offshore again• largely 67%• limited degree 33%• associated with lower PTSD symptoms(p

Background• PTSD is not a normal adaptation to severe stress.• PTSD is not an inevitable response to stress• most trauma-exposed (TE) people do notdevelop PTSD• many individuals will recover quickly from PTSD

PTSD: background• Recent studies in the USA report the lifetimeprevalence of PTSD at 8-12% (Kessler, 2000).– Prevalence rates vary markedly depending on methodology (0-12.3%)• Prevalence in Australia- 6.4% - most commonmental health disorder (Report on 2007 NationalSurvey of Mental Health & Wellbeing, Slade et al, 2009)• Prevalence in Europe varies– ESEMeD* study lifetime prevalence - 1.9% (Be, Fr, Ge, It, Sp, Ne)– Prevalence in NI – 8.8% - higher than other conflict areas,Ferry et al, 2011)– Switzerland – 0% (Hepp et al, 2006)*European Study of Epidemiology of Mental disorder, ESEMeD, Alonso, et al, 2004)

PTSD: background• ACTR Grampian pilot study lifetime prevalence5.4%• Approximately 80% of patients with PTSD willhave a co-morbid psychiatric condition, the mostcommon being:‣depression, drug and alcohol abuse, andother anxiety disorders

Resistance, Resilience & RecoveryAdapted from NATO, Psychosocial care for people affected by disasters & majorincidents, 2008

Resistance, Resilience & Recovery• People & communities show remarkable resilience• Up to 50% of people recover psychosocially withoutrequiring specialist intervention• This resilience allows for OPTIMISM but NOTCOMPLACENCY• However, also need to be aware of Ripple Effect

The victims include……• survivors• bereaved• family members• rescuers• emergency personnel• related colleagues• employers…….The “ripple effect”

Trauma-related risk factors• sudden, unexpected events• man-made rather than natural events• prolonged exposure• perceived threat to life• multiple deaths and/or mutilation• “dose response” relationship or proximity• personally relevant factors– such as the involvement of a child or identification withthe victim or family

Patient-related risk factors (i)• severe acute stress reaction• low serum cortisol increase acutely• family or personal history of mental disorder• serious physical injury (patient’s perception)• loss of normal daily function (such as employment)• extremes of age• genetic predisposition• Epigentics - transgenerational effects or previous trauma• past experience of trauma– especially childhood trauma

Patient-related risk factors (ii)• coping styles i.e., in charge of own destiny comparedwith feeling reliant on others• profound sense of hopelessness and powerlessness• personality traits such as especially anxious pre-trauma• behavioural problems before 15 years• lower educational, intelligence and socio-economic levels• life style leading to exposure to traumatic events• role of race may relate only to the above• female gender– but, primarily due to PTSD after violent assault

Environmental risk factors• lack of a support network (or inability toutilise it)• ongoing life stresses• reactions of others• (lack of) economic resources• disadvantage (whether social, educational oreconomic)• Displacement

Pre-traumatic risk factorsPersonal capabilities &attributes• Attachment capacity• Current attachments• Locus of control (i.e., in chargeof own destiny compared withfeeling reliant on others)• Gender (males cope better)• Extremes of age & development(children & older people)• Behavioural problems (

Peri-traumatic event factorsNature of the event• sudden, unexpected events• human-made rather thannatural events• prolonged exposure (e.g.,entrapment, hostage)• multiple deaths and/ormutilation• “dose response” relationshipor proximity• Nature of involvement(closer involvementincreases the risk)Impact of the event• perceived threat to life (selfor others)• Physical injury(real &/or perceived)• Extensive personal loss

Post-traumatic risk factorsResponses to the event• Nature of acute stressresponses• View of performance andown survival (survivor orperformance guilt)Burden consequent on theevent• Social &/or family supports• Displacement• Financial, social orrelationship problems orstrengths• Reactions from others(e.g., blame or rejection ofsuffering)

Normal reactions to trauma• numbness, shock, denial• fear• depression or elation• anger, irritability• guilt• impaired sleep• hopelessness, helplessness• cognitive and perceptual changes• avoidance• intrusive experiences (e.g., flashbacks)• hyperarousal, hypervigilance

Positive experience of trauma• approximately 2/3rds of survivors of PiperAlpha disaster described positive sequelae• example of cognitive reframing• From PRaCTICaL- many individuals reappraisinglife goals i.e., “what is important”– Many aim for return to work– a few delaying going back to work as see it asless important.

Myth• Post-traumatic Stress Disorder (PTSD) is themost important reaction post-traumaReality• PTSD is not even the most common reaction• Range of reactions• Some normal, some brief, some phasic, somechronic, some complex

Time Course of ReactionsTraumaticeventAcutestressreaction(first48 hrs)Acutestressdisorder(up to 4weeks)AcutePTSD(4-12weeks)ChronicPTSD(12 wks +)

Psychological reactions after trauma• Depression• Grief Reactions• Agoraphobia• Alcohol/Drug Dependence• Panic Attacks• Brief Hypomania• Specific Phobias (e.g., travel)• Post-traumatic Stress disorder(PTSD)

Specific populationsMayou et al (1993)RTA victims aged 18-70 years20% Acute Stress Syndromes10% Mood Disorders10% PTSD10% Phobic Travel Anxiety

PTSD by trauma type• Road Traffic accidents 10%• Burns 35%• Rape and sexual assault 57% (F)• Vietnam combat veterans 31% (M)37% (F)• Falklands War veterans 22%• Civil violence (NI) 23%• Mount St Helens 3.6%• Buffalo Creek Disaster 57%(14 years later) 25%• Bushfires 53%• Airplane crash 54%• Hurricane Andrew 33%• Piper Alpha disaster 73% (6/12)(10 years +) 21%• Firefighters exposed to 16%natural disasterBut, not all about PTSD, a range of disorders

A caveat• Most of the information we have is on adultvictims / survivors of traumatic events (TE)• From age of 8-10 years reactions closelysimilar to those manifested by adults• Below 8 (esp.

Childrens’ reactions• as with other anxiety disorders, children’s reactionsinfluenced by parental reactions– probably via both modelling /social influence– & inherited dispositions• Children sensitive to parents’ reactions- both to TEand talking about it• May choose not to describe event so as not toupset parent(s)• Show more overt aggression and destructiveness• Repetitive play about TE- repeated drawings of theevent

Collective identity“Holocaust survivor”“Piper Alpha survivor”“rape victim”“battered womansyndrome”“vietnam veteran”may contribute to:• longterm distress• stigmatisation• further victimisation• transgenerationaleffects

The “Double-think”The ability to hold two contradictory beliefs inones mind simultaneously and accept themboth (Herman, J.L., 1992) survivor and victim POW self and prior self safe world and being a victim (to blame or not toblame)

Introduction to TraumaticStress (part one)Assessment of post-traumaticreactionsDr Alastair HullUnited Kingdom Psychological Trauma Society, Regional Conference, City Hall, Cardiff, 2011

AssessmentTiming of Presentation• natural history of illness• at what point in course of illness• anniversary?• trigger?• why now?Is presenting problem the problem?Relieving/Exacerbating factors

Standard Clinical Interview• Thorough, not just core criteria for PTSD• do not think exclusively PTSD• sensitive, reassure only need snapshot atfirst interview• do not push too fast• can write it down if can’t talk

Standard Clinical Interview• Thorough, not just core criteria for PTSD• do not think exclusively PTSD• sensitive, reassure only need snapshot atfirst interview• do not push too fast• can write it down if can’t talk• be careful of statements “he didn’t seemat all upset as he spoke about theaccident”

Standard Clinical InterviewThis should cover the traumatic event in terms of:• when , how & where it happened• who was involved• how did the patient react• how did others react• Meaning of the trauma (e.g., core beliefs)• Meaning of the symptoms (e.g., indicate personalfailure)

Assessment• Purpose of Assessment– Diagnostic– Forensic– humanitarian– research/epidemiology• Therapeutic Alliance– trust, safety, confidentiality• 1 st Interview – critical in developing alliance– usual good interview practice– non-judgemental– allow ventilation– do not overcontrol -

AssessmentObjectivity• identification with the patient• recognition of own feelings• fear of being overwhelmed• own past history of trauma/lossUse of diagnostic interviews andstandardised self-report measures• may increase accuracy of formulation• increase accuracy of treatment efficacyreviews

Structured Interviews• Structured Clinical Interview for DSM III-R (SCID;Spitzer et al, 1990)• Clinican Administered PTSD Scale (CAPS;Blake et al, 1995)• PTSD Symptom Scale Interview (PSS-I; Foa et al,1993)• Structured Interview for PTSD (SI-PTSD; Davidsonet al, 1989)• MINI (Mini International NeuropsychiatricInterview; Sheehan et al, 1998)

Self-report Measures• The Impact of Event Scale-Revised (IESR; Marmer et al,1997)• Impact of Event Scale (Horowitz, 1979)• Davidson Trauma Scale (DTS; Davidson et al, 1996)• The Penn Inventory (Hammerberg, 1992)• PTSD-Symptom Scale (PSS-SR; Foa et al, 1993)• PTSD checklist (Weathers et al, 1993)• Mississippi Scale for Combat related PTSD (Keane et al,1988)

“Russian Roulette”• Survivors of life-threatening incidents takefurther risks because:• Invincible• Cope better the “next time”• Disguised attempt at suicide / “self harm”• Recapture the “buzz”

Patient Recall• “tunnel vision”• patients may misrepresent unintentionally• retrospective creation of memory• evolving nature of memory• patients commonly get wrong the timing andorder of events• gaps in memory? (especially if even minor head injury)• measure physiological arousal (if appropriate)

Nature of recall• ask how the memory progresses…is it like a video,or a freeze frame moving forward or a series of stillphotos, or just one.• this may give hints as to any memory loss, if memorysequential or any retrospective elaboration.• ask about all sensory modalities• check what they remember and what others havetold them.• ask what they don’t know but might like to.

Spouse or Partner• corroboration• explain typical reactions, avoidance ofcloseness or irritability etc.• how they can help• identify any “Ripple Effect”

Traumatic EventDSM• experienced, witnessed or confronted• threat of death or serious injury (self or others)• intense fear, helplessness or horrorICD• delayed &/or protracted response• exceptionally threatening or catastrophic• likely to cause pervasive distress in almost anyoneFor both the TE is the primary and overridingcausal factor

PTSD: ICD 10 Criteria• traumatic event(s)• repeated intrusive memories or dreams• against a background of “numbness” anddetachment• commonly, fear and avoidance of cues• usually, a state of physiological hyperarousal• only intrusive phenomena are essential for thediagnosis

PTSD: DSM IV Criteria• traumatic event(s)• intrusive symptoms: 1 or more• avoidance symptoms: 3 or more• increased arousal: 2 or more• duration 1 month• distress and impairment in social oroccupational functioning• acute / chronic / delayed onset

Intrusive phenomena• recurrent distressing recollections• nightmares• flashbacks, in any modality• distress accompanies reminders• physiological reactions (“fight orflight”)1 or more

Avoidant & emotional numbingsymptoms• avoidance of thinking or talking about the event• avoidance of reminders such as activities, places orpeople• amnesia for important aspect of trauma• loss of interest in activities• detachment• emotional numbing• sense of foreshortened future3 or more

Hyperarousal symptoms• sleep disturbance• irritability / anger• concentration difficulties• hypervigilance• exaggerated startle response2 or more

Associated symptoms• dissociative symptoms–depersonalisation, derealisation,awareness of surroundings, out ofbody etc.,• survivor guilt• performance guilt

The “Double-think”The ability to hold two contradictory beliefs inones mind simultaneously and accept themboth (Herman, J.L., 1992) survivor and victim POW self and prior self Safe world and being a victim but not to blame Pre and post-trauma self

Remember…..• positive experience of trauma• post-traumatic growth– with or without PTSD• impact of collective identity

Comorbidity• Approximately 80% of patients with PTSDwill have a co-morbid psychiatric condition• depression• anxiety disorders (including OCD)• alcohol misuse / dependence• drug misuse / dependence

Additional trauma-related diagnoses(ICD-10)Acute stress reaction• transient• mixed and changing clinical pictureAdjustment disorders• associated with symptoms of distress,anxiety and depression• predisposing and vulnerability factors playa significant role in developmentDissociative disorders• represents a collection of conditions suchas dissociative amnesia• onset and remission are often sudden• remit within a few monthsSomatoform disorders• repeated presentation of physical symptoms• may be reluctance to consider psychologicalorigins of symptoms• may be “attention seeking” behaviourEnduring personality change aftercatastrophic experience• end point of chronic PTSD• particularly severe stressor• hostile, suspicious, “on edge”, “different”• at least 2 years post-trauma

Introduction to TraumaticStress (part one)Conceptualisations &Models of PTSDDr Alastair HullUnited Kingdom Psychological Trauma Society, Regional Conference, City Hall, Cardiff, 2011

What must a model of PTSD Explain?• Precondition 1Must explain the 3 central constellations of problems in PTSD:re-experiencing phenomena; avoidance symptoms & hyperarousal.• Precondition 2Must account for the range of reactions to trauma: no apparentemotional sequelae; acute, chronic and/or delayed onset PTSD, naturalrecovery (or its failure)... etc.• Precondition 3Should be able to explain the effect of event variables, pre-morbidhistory of psychological problems, social support, attributional style andattitudes to emotional expression.

What must a model of PTSD Explain?• Precondition 4Account for the efficacy of treatments, especially exposure-basedtreatments.• Precondition 5To provide a coherent model of mind within which the above fourpreconditions can be realized.

Models /theories of PTSD• Conditioning Model (Mowrer, 1960)• Schema Theories (Horowitz, 1976; Janoff-Bulman, 1992)• Emotional Processing Model (Foa et al, 86; 89)• Dual Representation Model (Brewin et al, 96)• Cognitive Model (Ehlers & Clark, 2000)• Metacognitive Model (Wells, 2009)

Conditioning Model (Mowrer, 1960)• One of earliest paradigms applied was learning theoryi.e., classical conditioning• An attack seen as a unconditioned stimulus (UCS)• This evokes an unconditioned response (UCR; fear orpain)• Association learned (classically conditioned) betweenUCS and innocuous stimuli (CS; weather, hat, haircolour)• Once learned each CS evokes conditioned response(CR= fear)• So, learn safety behaviours (avoidance) to minimisefear

Conditioning Model (Mowrer, 1960)• Does not explain several key elements of fearacquisition and maintenance– Doesn’t explain numbing well or why some don’t get PTSD(especially flashbacks)• Reformulated stating CS & UCS are cognitivelyrepresented in long-term memory• So, avoidance not determined by experience offear BUT by individual’s expectation of whether agiven behaviour will protect from harm• N.B., can re-evaluate UCS in light of newinformation- so rape victim can re-appraisethreat after finding out another victim killed.

Conditioning Model (Mowrer, 1960)• Complemented by Learned helplessness model ofSeligman (1967) BUT even together don’t provide anadequate account of PTSD

Early Cognitive models of PTSD• Learned helplessness (Peterson & Seligman,1983)– similarity with victimization– generalised beliefs about future and its uncontrollability– futility of future responses• Learned helplessness (Abramson, 1978)– people seek to explain uncontrollable events on threedimensions:• Source (internal - external)• Temporality (stable - unstable)• Situational (global - specific)– those who make:internal / stable / goal attributions suffer moreexternal / unstable / specific attributions suffer less

Models /theories of PTSD• Conditioning Model (Mowrer, 1960)• Schema Theories (Horowitz, 1976; Janoff-Bulman, 1992)– i.e., theories from personality & social psychology• Emotional Processing Model* (Foa et al, 86; 89)• Dual Representation Model* (Brewin et al, 96)• Cognitive Model* (Ehlers & Clark, 2000)*models support imaginal exposure to greater or lesser extent

Horowitz: Stress response system• Horowitz provided an integration of psychoanalytic andinformation processing concepts• Suggested we have a basic need to match trauma-relatedinformation with “inner models” based on old information.• Leads to the revision of both sources of information untilthey agree/match• Called this the “Completion tendency”• Following trauma: information overload- completiontendency can not function• Defense mechanisms come into play to keep information inunconscious numbing and denial• Oscillatory state between intrusions and avoidance

Phases of response following trauma(Horowitz 1979)PHASESCommon states during each phase of responseT. EVENT OUTCRY States are high in arousal, emotion and actionDENIAL/ AVOIDANCEOSCILLATIONINTRUSIONWORKINGTHROUGHINCOMPLETE RESOLUTION= PTSDCOMPLETION /RESOLUTIONStates are lower in arousal and emotion as somememories or ideational implications of thestressor event are avoidedIntrusive ideas and images occur with pangs ofintense feelingOscillation occurs between states like thoseduring phases of denial and intrusion, withgradual reduction in the degree of avoidanceand sense of involuntary recollectionThe person returns to states like thoseexperienced before the stress inducing event

Just World Hypothesis• belief that we get what we deserve and deserve whatwe get. (Lerner, 1975, 1980; Lerner & Miller, 1978)• Links with Janoff-Bulman’s work (1985, 1989,1992)• 3 core beliefs (for most people):– World as benevolent,– world as meaningful,– the self as worthy• Underlying assumption is of justice and fairnessSHATTERED• NOT EVERY PERSON HAS THESE ASSUMPTIONS

Just World Hypothesis• However, some individuals hold negative pretraumaviews of themselves– TE confirms dysfunctional beliefs– Indeed, having such pre-trauma beliefs is a riskfactor for PTSD development• Conversely, strongly optimistic pre-traumabeliefs can act as a buffer to developing PTSD– Assumptions are not shattered

In additionResick & Schnicke (1993)• introduced idea that post-traumapsychopathology may result not just from afailure to accommodate trauma-relevantinformation BUT also from overaccommodationor assimilation of T-relevantinformation.

Problems with Schema theories• Why some get PTSD and not others• Late onset of PTSD• Initial denial and/or oscillations are notuniversal (Horowitz)• If ‘shattering of assumptions’ is theprimary mechanism by which TE producePTSD – problem for those with previoustrauma PLUS those with many previoustrauma would (from this theory) be expectedto recover quicker and they don’t

Emotional Processing Model2 central premises• PTSD centres around conditioned formation of a fear network inmemory following a traumatic event (TE)– This network or structure comprises• Stimulus information about the TE• Information about Cognitive, behav & physiological reactions to the event• Information linking stimulus & response elements– Leads to information processing biases (hypervigilance to T related stimuli)• Successful treatment modifies the pathological elements of thefear network / structure– Fear network / structure needs to be activated– New information that is incompatible with the erroneous information needsto be available and incorporated into this fear structure

Emotional Processing Model• Enduring appeal to many researchers• Model incorporates associations between stimuli & responses,associations bt stimuli and meanings associated with both stimuliand responses• Explains the efficacy of exposure therapy• Same mechanisms explain natural recovery and through therapy &why some recover whilst others do not• Also explains outcome despite pre-trauma assumptions about selfand world• Major limitation is its almost exclusive focus on fear- this isinadequate as a model of stimulus representation• Also struggles to explain dissociation and numbing

Cognitive Model(Ehlers & Clark, 2000)• Complex model building on previous cognitive models (& sharestheir strengths)• Based on concept of preponderance of data-driven processingrather than conceptual driven processing– i.e., XS negative appraisals, poor elaboration, maladaptive coping strategies• Integrate memory only if has lot of associations with personalthemes– Trauma memory lacks this contextual life• Avoidance seen as a result of a persistent sense of current threat• However, even during rapid TE meaning analysis reported (indeedthreat related interpretation is core!)

Cognitive factors in PTSD 1• During eventAutomatic detachment vs deliberate detachmentMental planning– protecting those with them– attract passers by– repeatedly saying to self I’m going to get through– deliberately detaching self• After eventNegative appraisal of actionsBlaming one’s actionsBlaming aspects of own personality

Cognitive factors in PTSD 2• Perception of other actions after eventNegative appraisal of how others responded• Victim’s interpretation of PTSD symptomsAppraisal of symptoms as incompetence or inadequacyNegative idiosyncratic interpretation of intrusions• Global negative belief about selfShattering of core assumptionsConfirming and reinforcing of previously held negativebeliefs

Models /theories of PTSD• Conditioning Model (Mowrer, 1960)• Schema Theories (Horowitz, 1976; Janoff-Bulman, 1992)• Emotional Processing Model (Foa et al, 86; 89)• Cognitive Model (Ehlers & Clark, 2000)• Dual Representation Model (Brewin et al, 96)*models support imaginal exposure to greater or lesser extent

Integrative model of adaptation totraumatic stressPERSONALITYSchemaAssumptionsNetworksConscious representationsRuminative processesof the eventEVENT EVENT COGNITIONS APPRAISAL MECHANISMS EMOTIONALSTIMULI Non-conscious representations Automatic processes STATESof the eventENVIRONMENTAL &SOCIAL CONTEXTTriggering cuesSocial supportCOPINGAvoidant strategiesActive strategiesJoseph et al, 1997

Dual Representation Theory of TraumaMemoryVerbally accessibletrauma memoriesIntrusive memoriesof conscious experienceEmotions related to traumaSelective recallStimuli Meaning analysis Selective attention Contents ofrelevantconsciousnessto priorPriorities fortrauma processing Selective attentionSituationallyaccessibletrauma memoriesFlashbacksDream materialTrauma specific emotionSelective recallPhysiological arousalMotor outputBrewin, Dalgleish & Joseph, 1996

Dual Representation Model(Brewin et al, 96)• Empirical testing in its infancy• However, it has the potential to make novel, testable hypotheses,not readily derivable from other theories• One issue of note however– Given the model you would expect interventions aimed separately at bothVAM & SAM to have better outcome-– however adding Cognitive restructuring to IE or in vivo exposure has notshown this (not enough of either perhaps?)

Introduction to TraumaticStress (part one)Neurobiology of PTSDDr Alastair HullUnited Kingdom Psychological Trauma Society, Regional Conference, City Hall, Cardiff, 2011

Genetics of PTSD• role of genetics starting to emerge• as of 2012 - 30 candidate gene studies• Vietnam Era Twin Registry (McCarren et al, 1995)• Twin study (Gilbertson et al, 2010) found significantly higherPTSD scores for TE twins c.f., non TE twins (p

Genetics of PTSD• Familial risk of PTSD partly mediated by geneticinfluences on exposure to trauma (Koenen et al, 2002)• Possible epigenetic role (modification of DNA inresponse to environmental influences) – role inintergenerational transmission (Yehuda & Bierer, 2009)• mixed evidence for specific genes– For example see Berenz et al, 2011– possible genetic marker for anxiety disorders (ch 15q; DUP25) linked withjoint hyperflexibility not replicated in UK for Panic or PTSD (St Clair et al,unpublished data)

A cautionary tale…..It is unwise to generalise betweendifferent trauma populations

Why should the therapistknow about neurobiology?• Understanding the underpinnings of posttraumaticreactions such as PTSD• Understanding how treatments mightexert their effects at a biological level• Patient psychoeducation• Credibility in eyes of the patient

Anxiety and Fear• a genetically ingrained function of the nervoussystem• NOT a sign of weakness• has adaptive evolutionary significance• promotes survival

Anxiety and Fear• emotion arises from neural processes that promptus to:– freeze (distant or inescapable threat)– or to flee (threat nearby and escapable)• much more than “fight or flight”– which implies a choice

Can differentiate “Freeze” furtherTo distant threat can be voluntary– i.e., “stop, watch and listen” pattern of vigilanceWhen ‘inescapable’ threat– “Tonic immobility” occurs– Involuntary state of profound (but reversible) motorinhibition– Especially when direct physical contact withpredator/ aggressor (Moskowitz, 2004)

Tonic immobility• 1/3- 2/3 of sexual assault cases• But not only this group• Features include– Decreased vocalisation– Intermittent EC– Rigidity and paralysis– Muscle tremors in extremities– Chills– Unresponsiveness to pain• May be associated with peri-traumatic dissociation

Tonic immobilityEnhances survival because……..• Evidence that predators less likely to attackimmobile prey• If attack, immobility may cause them to loosen gripincreasing chances of escape• Decreased risk of extreme violence which fightingback can cause• Some attackers lose interest if victim immobile andunresponsive

act first – or at least prepare(behaviour)……then think (cognition)

The Stress Response• acute stress leads to dose-dependent increase incatecholamines and cortisol• cortisol acts as to mediate (& shut down) the stressresponse• through negative feedback it acts on the pituitary,hypothalamus, hippocampus and amygdala• these sites are responsible for the stimulation of cortisolrelease• acute stress therefore increases cortisol levels• Biological paradox: cortisol levels are low in PTSD

Cortisol in PTSDDo lower cortisol levels in PTSD represent anaberrant response or a vulnerability prior to TE?• acute stress increases cortisol levels but, the rise in cortisol levelsis lowest in PTSD• chronic PTSD has low serum cortisol levels (Meewisse et al, 2007)• cortisol levels low at time of RTA in those later developing PTSD(McFarlane et al, )• cortisol levels in rape victims were found to be lower in those withprevious history of rape or assault (Resnick et al, 1995)• prospective studies are needed• preliminary studies have shown that children of holocaustsurvivors (with PTSD) have both a higher risk of developingPTSD and lower cortisol levels (Yehuda et al, 1998 & 2000)

Neurobiology of threat• Increased proximity to a predator shifts brain activationfrom prefrontal cortex to the midbrain periaqueductalgray– region responsible for active & passive defence responses(Mobbs et al, 2007; Bandler et al, 2000)– When feel under threat (as opposed to feeling safe) get a shift fromcortical to subcortical activation (Butler et al, 2007)• PTSD is thought to be associated with a deficiency in top-downmodulation of amygdala activation by the prefrontal cortex(Simmons et al, 2011)• Ability to regulate emotional responses to negative stimuli maybe protective factor when exposed to trauma – a resilience factor(New et al, 2009)

Orientating response• Arousal• Arrest• Alert-unfamiliar stimulus registers in nervous system-pause in or slowing of movement and activity-all senses heightened (to take in more information)• Muscular change -both flexion & extension• Orient/scan• Locate• Identify• Evaluate• Take action-search for the location (“where is it”)-source of the stimulus is found-novelty is recognised &/or identified-what is it? Is it dangerous/friendly? Do I pay attention?-not dangerous, normal activity resumed• Reorganise-dangerous- defensive or emergency sequence activated-the nervous system re-equilibrates

Orientating response variesaccording to …..• Nature of the stimulus– abrupt or gradual– familiar or unfamiliar– e.g., if auditory- sense of hearing hyperalert etc….• Internal state of the person– existing arousal level– level of consciousness– configuration of mental / emotional / physical components• The person’s previous experience– especially past traumatic experience

Arousal zonesHyperarousal zonesympathetic “fight orflight” responseWindow of toleranceOptimal arousal zonesocial engagement response(ventral vagal)Hypoarousal zone“immobilisation” response

The Triune BrainReptilian brain• body regulating, unconsciousOld mammalian brain• limbic system plus reptilian brainNeo-mammalian• cortex, plus the limbic system, plus the reptilian brainEach layer elaborates the more primitive layer.e.g., the reptilian brain in humans is more flexible in humansbecause it has access to the limbic system

Bottom-up & Top downProcessing led by either• Mammalian brain-– “top-down” processing• Reptilian brain– “bottom-up” processingacting on fear response,physiological mechanisms,can’t orientate to other things,all about escape

Biological findings in PTSDPhysiological changes include:• non-habituation to acoustic startle stimuli• extreme autonomic responsiveness to stimuli• increased heart rate and blood pressure• enhanced skin conductance and electromyogram responsesto stimuli

Biological findingsDysregulation of:• noradrenergic /catecholamine systems• serotonin system• HPA axis, especially corticotropin-releasing factor & cortisol• endogenous opioid system• immune response to trauma• gamma-aminobutyric (GABA)-benzodiazepine system• excitatory amino acid system (glutamate)• thyroid function• Neuropeptide Y

Brain areas of interest in PTSDHippocampus• knowledge of its role in declarative or explicitmemory (VAM) and the stress responseAmygdala• role of fear during both the trauma and itsrecollection• pre-clinical evidence for role of amygdala in fear

Decreased hippocampal volumevariable vulnerability?• bilateral reduction• right sided (adult trauma)• left sided (childhood trauma e.g., CSA)• no difference between early (8 years) of childhood abuse• N.B., distressing cancer-related recollections (left sided)• changes not demonstrated within 6 months of trauma• MZ twin study suggesting smaller hippocampal volumeis a risk factor for PTSD (genetic or environment?)(Gilbertson, 2002)• this may explain an apparent biological paradox

The biological paradoxThere is an apparent paradox at the heart ofneurobiological and imaging studies of PTSD• high cortisol levels damage the hippocampus (McEwen etal, 1992)• but, cortisol levels are low in PTSDSuggested explanation• receptors for cortisol are more sensitive in people withPTSD -at the level of the pituitary gland (Yehuda, 1995)

Other hippocampal findings• Current (not lifetime) PTSD symptom severityexplains hippocampal size (Apfel et al, 2010)• We found hippocampal size correlated withseverity of PTSD (Minhas et al, 2003; 2004)• Possible explanations– Small hippocampus is a risk factor for lack of recoveryfrom PTSD (trait)– OR, PTSD effects on hippocampal volume arereversible once the patient recovers from PTSD (state)

Decreased hippocampal volumeassociated with:• bipolar disorder*• aging preceding dementia• dementia• Cushing’s syndrome• alcohol misuse• borderline personality disorder• In all of the above associated with elevated GC levels• GC-induced atrophy appears to require prolonged or repeatedbursts of GC excess (in combination with other neurochemicals)* Effect vanishes if control for childhood abuse

Other structural findingsBrain tissue loss• increased Ventricular Brain Ratios found in adults (3studies) and in children (1 study)• In children,‣ PTSD associated with increased ventricular volume, andwith reduced cerebral and corpus callosum volumes‣ Brain volume correlated with age of onset of traumaand negatively with duration of abuse‣ PTSD subjects also had lower verbal and performanceIQs

Limbic systemslowMoreelaborateprocessingofwholeobjectvisual auditory kinesthetic gustatory olfactory

Brain areas of interest in PTSDHippocampus• knowledge of its role in declarative or explicitmemory and the stress responseAmygdala• role of fear during both the trauma and itsrecollection• pre-clinical evidence for role of amygdala in fear

Main functional findings:• Abnormalities of limbic and paralimbic areas duringsymptom-provocation especially the amygdala– N.B., not universal finding (e.g., Britton et al, 2005)• thought to be related to role in mediating emotionalarousal• PTSD may represent the failure of medial prefrontal/anteriorcingulate networks to regulateamygdala activity• results in hyper-reactivity to threat

Amygdala activation• subjects with Alzheimer’s disease• remembered their personalexperience rather than the contextof the earthquake• Impairment of emotional eventmemory is related to amygdaladamage• irrespective of generalised brainatrophy and cognitive impairments(Ikeda et al, 1998; Mori et al, 1999; Kazui etal, 2000)

Other functional findingsIncreased rCBFposterior cingulate• may relate to its role inthe emotional processingof distressing materialcerebellar tonsil• may be associated withfear responseAbsence of anteriorcingulate activity• may be associated withinability of people withPTSD to extinguish fear

Implications for Treatment?“In order for the amygdala to respond tofear reactions, the prefrontal region hasto be shut down...(treatment oftraumatic memory) may require that thepatient learn to increase activity in theprefrontal region so that the amygdalais less free to express fear”121(LeDoux, 2003)

Other significant functional findingsNeuronal activity underlying dissociation (Lanius et al,2005)• all patients in “dissociative” group exhibited dissociativeresponses to trauma script-driven imagery (e.g., out of body)• all in “reliving” group described being back at the scene• Non-PTSD described ordinary autobiographical memory• differences in physiological measures (e.g., heart rate)• Clear differences in functional connectivity shown between thegroups– may represent altered conscious experience– Ventrolateral Nucleus of thalamus (its stimulation results inlanguage processing abilities – “unspeakable” nature?)– non-verbal response to the memory?– Changes in insula (role in perception of internal states)

Emotional stroop paradigmCo-investigators: Mario Liotti, Annalena Veneeri &David A. Alexander• comparison of subjects with PTSD, panic and matchedcontrols• neuropsychological assessment indicates a very specificdeficit in topographical memory (right sided function)• Correlates with hippocampal volume reduction• screening for possible genetic marker• functional MRI scan– block design with emotional and neutral words– looking at anterior cingulate activity (i.e., to see ifsubjects have the ability to extinguish fear)

Emotional stroop paradigmSatvir Minhas, Alastair Hull, Mario Liotti, AnnalenaVeneeri & David A. Alexander• comparison of subjects with PTSD, panic and matchedcontrols• neuropsychological assessment indicates a very specificdeficit in topographical memory (right sided function)• Correlates with hippocampal volume reduction• screening for possible genetic marker• functional MRI scan– block design with emotional and neutral words– looking at anterior cingulate activity (i.e., to see ifsubjects have the ability to extinguish fear)

Emotional stroop paradigmResults• neuropsychological assessment indicates a veryspecific deficit in topographical memory– both for localisation and landscape recognitiontests• Regional atrophy in bilateral orbitofrontal cortexand right hippocampal region• Atrophy correlated with PTSD symptom severity(Minhas, Hull, Liotti, Veneeri & Alexander, 2003; 2004)

Summary of main findings• hippocampal atrophy• increased activity of the amygdala and other limbicareas• deactivation of Broca’s area when individual’s accesspersonal traumatic memories• right-hemispheric lateralisation• confirms neuropsychological tests demonstrating deficits inright sided cognitive function e.g., topographical memory• may explain the “timeless” quality of traumatic memory• an artifact of small samples, or gender?• Decreased activity pre-frontal & cingulate cortex

Clinical relevance• Encouragement to “move on” may bestigmatising as not all responses to trauma allowthis• i.e., for some the biological stress response has not beenproperly terminated• time is not necessarily always a great healer• inappropriate to “wipe the slate clean”• “unspeakable”• importantly, the reactivation of memorydoes not require it to be put intocommunicable language

Clinical Implications• PTSD is not a normal adaptation to severe stress• Psychoeducation reduces impression of weakness• exaggerated startle response is not a sign of cowardice or timidity• Fear response including “tonic immobility” not a sign of cowardice• corrective information about fear response• Tonic immobility =/= consent• Out of body experience• Physiological response to abuse• relatives need Psychoeducation too!

Implications• Resilience to stress– Need to have graded exposure to predictable, controllable stressthisdecreases stress sensitivity– N.B., physical exercise improves stress resilience• Why psychotherapy if brain affected– Information about NI studies pre and post• Hippocampal damage– Unclear if result of TE, PTSD or risk factor– N.B., Vermetten et al (2003) – SSRIs increase hippocampalvolume in people with PTSD– Bendel et al (2005) – hippocampus can regenerate lost neurons

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