TRAUMA AND PTSD SOUTH AFRICA

Dan J. Stein

University of Cape Town

OVERVIEW

• Some background context

• Some epidemiological data

• Some neurobiological data

• Some quasi-interventional data

CONTEXTPolitical

• 1948 - National Party comes to power• 1976 - Soweto schools’ uprising• 1990 - Nelson Mandela released • 1993 - Interim Constitution negotiated• 1994 - ANC democratically elected• 1995 - Promotion of National Unity and

Reconciliation Act

CONTEXTPersonal

• 1986 - Completed medicine at UCT

• 1991 - Completed psychiatry in NYC

• 1994 - Completed Fellowship on OCD

• 1997 - MRC Unit on Anxiety & Stress

• 2005 - Moved to UCT as Head of Dept

CONTEXTScientific

• 1800s - Psychiatric asylums• 1950s - University Depts of Psychiatry• 1960s - Papers on behavioral Rx • 1970s - Academic boycott• 1990s - Academic collaboration• 2000s - First fMRI/neurogenetics• 2010s - Global mental health funding

CONTEXT:Psychiatry

CONTEXT

• In some ways, the context of South Africa is quite unique

• But also, reminiscent of aspects of USA and of low-middle income countries

• A fascinating laboratory for the study of trauma and PTSD!?

EPIDEMIOLOGY

• South African Stress & Health Study (SASH)

• First nationally representative psychiatric epidemiology study in Africa

• n = 4351, rigorous probability sample design

• Similar design to other countries in the World Mental Health Surveys (WMHS)

EPIDEMIOLOGY

• In this setting, what are the potentially traumatic events (PTEs), and what is their conditional risk for PTSD?

• Methodology assessed PTSD in relation to both a random PTE and in relation to most severe PTE

Lifetime Prevalence of Psychiatric Disorders in SA

B C W I

Anxiety disorder 16.5 15.7 11.9 11.3

Mood disorder 9.6 10.3 8.6 13.2

Substance disorder 12.6 18.9 15.0 5.5

Any disorder 30.1 35.5 26.5 26.2

(Stein et al, 2008)

• Psychiatric disorders are more disabling than physical disorders

• Psychiatric disorders are 10 times less likely to be diagnosed and treated

• The relative burden of PTSD refers to the %age of all months lived with PTSD in the pop due to episodes associated with a PTE.

• Represents a combination of three factors: the prevalence of the PTE, conditional risk of PTSD, and the PTSD duration.

Traumatic Events by Category

Relative PTSD Burden

Why is Witnessing Important?

• A common trauma with low PTSD risk can be very burdensome (e.g., MVAs)

• In specific context of South Africa, there have been many community protests

(Atwoli et al, 2012)

Further Analyses of Witnessing

• Witnessing associated with exposure to a higher number of traumatic events

• PTSD, mood, and anxiety disorders varied significantly with witnessing status

(Atwoli et al, 2015)

• Dissociation is associated with greater severity and greater impairment

• In the WMHS dataset as a whole, there are also universal themes

Practical Relevance

• Clinicians should be aware that some traumas are less common in the clinic, but more important for public health

• Clinicians should be aware of the dissociative subtype of PTSD, and its association with greater severity

Capacity Building / Next Steps

• SASH and WMHS provided numerous opportunities for students

• Several PhDs (e.g., Sorsdahl, Atwoli)

• Dozens of publications (including e.g., collaborations with Prof Ndetei)

Capacity Building / Next Steps

• Harvard-UCT Neurogenetics of African Populations (N-GAP) study

NEUROBIOLOGY

Hippocampal Glucocorticoid Receptors in Stressed Rodents

(Uys et al, 2005)

PTSD - MRI

(Seedat et al, 2004)

PTSD – functional imaging

PTSD – MRI

(Vermetten et al, 2003)

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Left Hippocampus Right Hippocampus

Hipp

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m-3

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BaselinePost-treatment

NEUROBIOLOGY

Urbach-Weithe Disorder

• 37 patients with UWD (>10% of the world population) compared to controls

• UWD was associated with high prevalence of anxiety disorders

• UWD was associated with impairment in executive functions

(Thornton et al, 2008)

Urbach-Weithe Disorder

• This initial picture was somewhat counter-intuitive

• But there is increasing basic knowledge of amygdala subregions

• Does this “natural lesion” provide a picture consistent with this knowledge?

Structure (BLA) vs Function (S/CMA)

UWD patients recognize fear better

UWD patients attend to fear longer

Role of the BLA

• BLA often seen as the “sensory” amygdala, with input from thalamus/PFC

• Inhibitory functions of the BLA on the CMA increasingly recognized

• Speculatively, BLA underlies goal-directed rather than reflexive responses

(Terburg et al, 2012)

UWD show generous investment

(van Honk et al, PNAS, 2013)

UWD patients with improved WM

(Morgan et al, Plos One, 2012)

Evolutionary Speculation

• Orientation to salience is rapid, involuntary and effortless, whereas executive inhibition of bottom-up interference is effortful

• Evolutionarily advantageous for PFC to be able to override amygdala-mediated “false alarms” during goal-oriented cognition

(Morgan et al, 2012)

Practical Relevance

• Clinicians should recognized that trauma- related symptoms are normal and adaptive; people are enormously resilient

• It may be useful for clinicians to explain PTSD to their patients as an amygdala-mediated false alarm

• Alarms can be useful, but in PTSD a range of different clinical interventions are helpful in turning the alarm threshold lower

Capacity Building / Next Steps

• Students in MRC Unit have developed a number of animal models

• Cape Universities Brain Imaging Centre (CUBIC) has hosted numerous students

• Particular focus has been on neuroHIV, substance use disorders

Capacity Building / Next Steps

• New opportunity is ENIGMA e.g. ENIGMA-HIV, ENIGMA-PTSD

AN INTERVENTION: THE TRC

Origins of the TRC

• to promote national unity and reconciliation in a spirit of understanding

• to detail the nature, causes, and extent of gross human rights violations

• to facilitate amnesty to perpetrators who fully disclose politically motivated acts

Origins of the TRC

• to restore human and civil dignity by giving victims a chance to relate violations

• to report back to the nation, recommending reparations

• to recommend steps to safeguard future prevention of violations

Origins of the TRC

• a negotiated political settlement

• retributive justice de-emphasized

“S.A. has decided to say no to amnesia and yes to remembrance; to say no to full scale procecution and yes to forgiveness”

Truth and Reconciliation:Themes to Consider

• Psychological effects of discrimination

• Providing services and help for survivors

• Understanding the nature of perpetration

• Human rights in psychiatric practice

(Stein et al, Br J Psychiatry, 2000)

Truth and Reconciliation:Helping Survivors

• The TRC as an enabler of catharsis or “testimony therapy”

- evidence for “testimony therapy” - clinicians on the TRC

Truth and Reconciliation: Helping Survivors

• Secondary traumatization by a once-off unsympathetic exploration of the past

- lack of clinical resources - lawyers on the TRC

Truth and Reconcilation:Methods

• SUBJECTS: Xhosa-speaking survivors of gross human rights violations, with and without participation in the TRC

• INTERVIEW: HRV instrument, MINI psychiatric diagnosis, Enright Forgiveness Inventory

Truth and Reconciliation:Methods

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PublicTestimony

ClosedTestimony

No Testimony

Truth and Reconciliation:Results

• PTSD was predicted by human rights violations

• However, severity of PTSD and PTSD comorbidity were predicted by human

rights violations, civilian traumas, multiple stressful life events, and gender

Truth and Reconciliation:Results

• No significant association between TRC participation and psychiatric status

• Presence of depression (p=.01), PTSD (p=0.03), and other anxiety disorders (p=0.04), significantly correlated with lower forgiveness scores

SASH data on the TRC

• Psychological distress was significantly associated with having a TRC related experience to share, and with negative perceptions of the TRC

• The majority of South Africans viewed the TRC moderately positively, irrespective of age, education, and race

(Stein et al, 2009)

Truth and Reconciliation?

Helping Survivors

• The TRC may have misled by promising too much, and is unlikely to have helped those with disorders like PTSD

• However, the TRC provided dignity and “acknowledgment” to many; a lesson in social approaches to distress

(Stein et al, 2008)

Practical Relevance

• Social context plays a key role in influencing the response of individuals to trauma

• Good leadership can be crucial in the aftermath of trauma, at institutional level or at governmental level

Capacity Building / Next Steps

• With global mental health funding there are now opportunities to do clinical trials

• Several of these are now ongoing in the Dept of Psychiatry at UCT

• They include work on participants with trauma exposure

Capacity Building / Next Steps

• Drakenstein Birth Cohort Study may be a particularly useful foundation

CONCLUSION

• Epidemiological data from SA provide unique and universal lessons

• Laboratory and clinical data have contributed to models of PTSD

• Rare UWD population may be useful for studying amygdala function

• The TRC provided important lessons that may have broader applicability

CONCLUSION

• We have worked from bench to bedside to beyond

• Capacity building has been a core component of our research

• Significant opportunities for future cross-country collaboration (e.g., N-GAP)

• Psychopharmacology conference (Nairobi Oct 9/10, sonja@londocor.co.za)