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Kim Felmingham

School of Psychological Sciences

University of Melbourne

kfelmingham@unimelb.edu.au

The Neurobiological and Cognitive Impacts of 

Trauma

Outline

• Impact of childhood trauma on psychological functioning

• Neurobiological impact of trauma/PTSD – in adults and children

• Cognitive impact of trauma/PTSD in adults and children

• Critical sensitive periods of development and trauma

• Implications for treatment

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Prevalence of Childhood Trauma Exposure (WHO, 2014)

• World Health Organization (WHO, 2014) global survey included 133 countries, covering more than 6 billion people: 

• • 1.3 million people die each year as a result human inflicted violence 

• • More than 25% of all adults reported physical abuse as children 

• • Nearly 1/5 women (18%) and 1/10 men (7.6%) reported childhood sexual abuse 

• • Traumatic experiences not random

– –gender (female), poverty, minority groups, are all more vulnerable (Harvey, 2007)

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Adverse Childhood Experiences (ACE) research

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Dube et al., 2003, Pediatrics

1 in 4 women, 1 in 6 males reported childhood sexual abuse (Dube et al., 2005, Am J Prev Med)

40% of ACE samples experienced > 2 Adverse childhood experiences

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Childhood Trauma and Adult Mental Health

• Well recognized in both retrospective and prospective studies that childhood trauma is a major risk factor for many psychological disorders

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Major Depression

PTSD

PsychosisBPD

Substance Abuse

Childhood Trauma

Scott et al., (2010) Arch Gen Psychiat, Green et al, (2010) Arch Gen Psychiat, Etain et al., (2010) J Trauma Stress, Cougle et al., Psychiatry Res, Mayo et al., (2017) Neurosci Biobehav Rev; Bryant et al., (2010)

Childhood trauma accounts for approx. 45% of population attributable risk for psychiatric disorders (Teicher & Samson, 2016)

Graded dose-response relationship between number of ACE experiences and mental health outcomes

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Merrick et al., 2017, Child Abuse and Neglect

Multiplicity of Childhood Trauma – Effects on Psychological Functioning

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ACE individual contributors to mental health

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All ACE’s except physical neglect

Adult Illicit drug use

All ACE’s except parental divorce and jail

Adult heavy drinking

All ACE’s except parental jail (esp emotional abuse, 

neglect and parent mental illness

Adult Depression and suicide attempts

‐ Childhood sexual abuse a significant predictor across the board of all disorders‐ Exposure to one childhood trauma increases risk of exposure to another‐ Cumulative risk for adult mental health problems with each additional ACE

Merrick et al., 2017, Child Abuse and Neglect

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Person-Centred Approach – Systematic Review of Latent Class Analyses

• Given the evidence of:

– cumulative effect of trauma exposure, 

– that exposure to one childhood trauma increases the risk of exposure to further childhood traumas, 

– recognition that trauma doesn’t occur randomly but in patterns 

Recent studies have employed latent class analyses to examine individual patterns of trauma exposures and identifying if there are specific factors associated with patterns of trauma that predict later mental health

• We recently conducted a systematic review of LCA studies of patterns of trauma exposure

• We reviewed 17 LCA studies (12 which recorded childhood trauma exposure, alongside adolescent and adult trauma exposure)

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LCA findings relating to adult trauma exposure

• 3 latent classes of trauma exposure

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Low probability of trauma exposures

High probability of interpersonal trauma exposure (esp sexual 

trauma)

High probability of witnessing trauma and 

physical assault

Good mental health

Increased risk of PTSD, AOD, 

psychosis, bipolar, panic and MDD

O’Donnell et al., 2017, Clin Psych Rev

female

male

LCA findings in relation to childhood trauma exposure

• Two latent classes found:

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High exposure to multiple traumas ‐

Low exposure to trauma

Increased risk anxiety and affective disorders (if class membership characterized by sexual 

abuse)

Increased risk of alcohol and substance use disorders (if class 

membership characterized by physical assault)

Normal mental health

* Impact of gender less clear in childhood trauma analysis – 5/12 studies showed no gender effect.  When gender effect present females more likely to be member of class characterized by sexual trauma, emotion abuse and multiple trauma.  Males more likely in class characterized by physical abuse.

More likely to have mental health problems if trauma occurred 

within the home than community

O’Donnell et al., 2017, Clin Psych Rev

Childhood Trauma

• Involves repetitive or prolonged exposure to, or experience of multiple traumatic stressors, often of an interpersonal nature

• Involve harm or abandonment by caregivers or other responsible adults – dysregulations in attachment

• Occur at developmentally vulnerable times, especially in the course of childhood, and become intertwined with a child’s biopsychosocial development.

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Cloitre et al., 2006, Treating Survivors of Childhood Abuse

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Theoretical Models Childhood Trauma – Resource Loss Model

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Cloitre et al., 2006

Childhood trauma affects clinical symptom presentation - PTSD and Complex PTSD

• Clinicians have long argued that PTSD doesn’t capture the complex symptoms of distress associated with childhood trauma (Herman, 1992) 

– Complex PTSD to be introduced in the ICD‐11 in 2018 

– Dissociative PTSD subtype in DSM‐5  (PTSD plus high derealisation or depersonalization)

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PTSD Symptoms

Emotion Dysregulation

Interpersonal/attachment dysfunction

Negative Core Beliefs

Cloitre et al., 2006; 2014

Adult versus Childhood, Single vs multiple trauma exposures on psychological functioning

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Multiple traumas have significant greater effect on dissociation (regardless of childhood or adulthood), childhood trauma greater shame.  No significant difference on depressive symptoms (Haagenaars et al., 2011, J Affect Dis)

Dissociation Shame

Neurobiological Effects of Trauma/PTSD

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Williams et al., 2006, Neuroimage

Bryant et al., 2008, Psych Med

Felmingham et al., 2010, J Abnormal Psych

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Fear Circuitry Model of PTSD

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Meta‐analysis 79 PTSD fMRI studies

Hyperreactivityamgydala, insula, DACC

Hyporeactivity –hippocampus, VMPFC

Hayes et al., 2012

Fear circuitry Model of PTSD

Impaired vmPFC and HC inhibitory input onto amgydala fear processing (and fear conditioning) pathways (Yehuda et al., 2015, Pitman et al., 2012, Nat 

Neurosci Rev)

Emotional Undermodulation (excessive fear circuitry) and Emotional Overmodulation (Dissociative PTSD– childhood trauma) both in PTSD

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Yehuda et al., 2015, Lanius et al,. 2012

Brain regions impacted by trauma/PTSD

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Increasingly recognized PTSD not just a disorder of fear circuitry

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Evidence of more distributed dysregulation in salience and default mode networks in PTSD

Greater activation in insula, dorsal ACC, and functional connectivity in salience networks in PTSD (Aupperle et al., 

2012; Aupperle et al., 2013)

Reduced connectivity in default mode network(Daniels et al., 2011, Journal of Psychiatry and Neurosci.)

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Neurobiological Effects of Childhood (Complex PTSD) vs Adult (PTSD) in Adults

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Neurobiological Effects of Childhood Vs Adult Onset trauma in adults with PTSD

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CPTSD > PTSD (Fear vs neutral faces)

Right Precuneus

L ParahippocampalGyrus

Dorsal, rostral ACC

Bilateral Insula

L Orbitofrontal/ VMPFC

Bryant, Felmingham et al., 2019,  under review.

Neurobiological Effects of Childhood vs Adult Onset Trauma in Adults with PTSD

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Greater amygdala and prefrontal cortical activation in childhood PTSD than adult onset PTSD despite equivalent symptom severity(Bryant, Felmingham et al., 2019,  under review)

Childhood trauma exposure/complex PTSD associated with greater amygdala reactivity, insula, parahippocampal gyrus, dorsal ACC and orbitofrontal activation to fearful faces than adult‐onset PTSD

Trauma exposure alone has significant impact on brain function (independent of PTSD)

PTSD vs all controls PTSD vs Trauma‐exposed controlsEffects of PTSD 

PTSD vs Trauma‐naïve controlsEffects of PTSD and trauma exposure

• Differences: Specific Effects of Trauma-Exposure? Includes precuneus, ventral PFC

Stark et al., (2015), Neurosci BioBehavReviews

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Childhood Trauma – Developmental Effects on Brain

• Childhood trauma may increase risk for psychopathology by serving as an early life stressor which induces epigenetic modifications which reprogram the stress response, and downstream processes (synaptic pruning, neurogenesis, myelination) which then alter the trajectories of brain development.

• Developmental trauma impacts on brain structure, function, connectivity and network architecture, with particular effects in :

– Hippocampus

– Anterior cingulate cortex

– Amygdala

– Corpus callosum (Teicher et al., 2016)

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Childhood Trauma Effects on Structural Brain Volumes

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Adults with history of childhood trauma show increased amygdala volume, and severity of trauma accounted for 27% of the variance in amygdala volume 

Teicher et al., 2016, Nat Rev Neurosci

Childhood Trauma Effects on the Brain in Adults _Structural Connectivity

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Greater connectivity in left anterior cingulate and other nodes for unexposed controls relative to adults with maltreatment histories (ACC governs affect regulation)

Greater connectivity in right anterior insula (arousal, interoceptive awareness) and right precuneus (self‐referential processing and episodic memory) in adults with childhood trauma histories compared to controls

Teicher & Martin, 2014,  BiolPsychiatry

Event-Related Potential Findings: Childhood versus Adult Trauma in healthy adults

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Standardized facial emotion expression datasets (Gur et al., 2002)

Showing blocks of emotional faces –angry, neutral, happy, fearful under two conditions:

Conscious (presented for 500 mseach)

Non‐conscious (backwardly masked –presented for 16 ms, followed by 150 ms neutral mask)

Event‐related potentials recorded during processing of faces

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ERP to Facial Expressions

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ERPs are high temporal resolution measures (milliseconds) recording real‐time electrical brain activity during a task.

Measures cortical function from scalp EEG, time‐locked to stimuli and averaged

Waveform of facial ERP – P100 amplitude reflects very early selective attention, N170 amplitude reflects structural encoding/processing of facial expressions

Childhood trauma exposure vs adult trauma exposure on face ERPs

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N170 amplitude failure to discriminate between angry and happy facial expressions in adults surviving childhood interpersonal trauma (dashed line) relative to those who did not experience childhood trauma 

Chu et al., (2015) J Psychiat Res

Face ERPs to dissociative and non-dissociative PTSD

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Dissociative PTSD group displayed significant greater N120 amp than non‐dissociative to all facial expressions (didn’t discriminate threat from non‐threat)

Dissociative PTSD displayed reduced VPP amplitude to happy faces

Klimova & Felmingham, 2013, Eur J Traumatology

Impact of Trauma/PTSD on neural activity in children

• Examined fMRI BOLD responses to threat and neutral images in 24 healthy youth (mean age 14) and 24 youth with PTSD (mean age 14)

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Greater activity in dorsal ACC (fear expression) to threat vs neutral images in PTSD

Reduced vmPFC‐amygdala connectivity to threat in PTSD compared to controls –reflects impaired regulation over threat processing networks

Wolf & Herringa, 2013, Neuropsychopharmacology

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Longitudinal impact of trauma exposure on neurobiology in children

• First longitudinal, multimodal neuroimaging study of children with PTSD compared to healthy controls (age 14 at baseline scan, age 15 at 12-mth follow-up)

• Structural MRI and resting state FMRI

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PTSD kids had reduced grey matter volumes in vmPFC and ventrolateral PFC than controls

Reduced PFC_amygdala, and PFC‐Hippocampal connectivity over time in PTSD, increased connectivity in healthy controls

Heyn et al., 2019, Neuropsychopharm

Cognitive impact of trauma exposure/PTSD in adults

• Significant amount of neuropsychological research reveals cognitive deficits in PTSD

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Meta‐analysis of 60 neuropsychological studies in PTSD vs controls (n=4108) reveals largest effect sizes of deficits in verbal learning (d=‐.62), speed of information processing (d=‐.59), attention/working memory (d=‐.50), and verbal memory (d=‐.46) for PTSD compared to controls

Cobb‐Scott et al., 2015, Psych Bull

Cognitive impact of trauma exposure/PTSD in children

• Meta-analysis of 27 neuropsychological studies in children (n=1526 participants – 416 with PTSD, 420 trauma-exposed controls, others non-trauma exposed)

• PTSD vs controls– Large effect sizes revealing deficits in PTSD vs controls in

• General intelligence (d=-.88)• Language/verbal function (d=-.65)• Visuospatial function (d=-.53)• Speed of information processing (d=-.62)• Learning and memory (d=-.67)• Executive function (d=-.52)

• PTSD vs trauma-exposed controls• General intelligence (d=-.28)• Visuospatial function (d=-.42)

• Trauma-exposed vs non-trauma exposed controls• Executive function (d=-.23) poorer in trauma exposed• Learning and memory (d=-.61) poorer in trauma exposed

• Trauma-exposed kids showed cognitive deficits compared to controls, but greater deficits seen in those with PTSD diagnosis

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Malarbi et al., 2016, Neuroscience Biobehav Rev

Stress toxicity models of developmental trauma (Shonkov et al., 2012; Teicher et al., 2014)

• Toxicity models of developmental trauma argue that childhood and adolescent trauma experiences interact with genetic vulnerability, and epigenetic activation to trigger a cascade of stress reactions which impact the development of stress‐sensitive neural regions (Hippocampus, Amygdala, PFC) typically which are associated with high glucocorticoid receptor density.

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Genetic Vulnerability

Trauma Exposure /epigenetics

Stress response cascade –cortisol (HPA), noradrenaline (SNS), vasopressin‐oxytocin

Impaired development stress sensitive neural regions (PFC, Amygdala, 

Hippocampus)Shonkov et al., 2012; Teicher et al., 2014

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Stress-sensitive neural regions

• Stress sensitive neural regions are very similar to regions impacted by trauma/PTSD in fear circuitry model

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Critical Sensitive Periods – Windows of Vulnerability – Early Adolescence

• It is recognized that early adolescence and puberty is a sensitive period with heightened risk for vulnerability for risk of mental health problems (Ladouceur et al., 2012)

• Anxiety disorders typically develop and emerge over late childhood and adolescence

• Puberty is associated with substantial changes in terms of social and physical development, hormonal influence and related neurobiological development.

• Activation of the Hypothalamic-Pituitary-Gonadal (HPG) system, and increase of estradiol and testosterone, is associated significant neural changes

• This brain development is directed by genetics, but sculpted by experience especially during these critical sensitive periods – therefore, if trauma exposure occurs during a sensitive period, potentially has a magnified effect

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Teicher et al., 2016; Shonkoff et al., 2012

Differing windows of neurobiological vulnerability with age

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Different neural structures implicated with trauma and stress responsivity develop maturationallyat different ages, with associated increases in vulnerability 

Hippocampal vulnerability to trauma peaks early (ages 2‐4)

Amygdala vulnerability to trauma peaks in early adolescence (ages 10‐12)

PFC vulnerability to trauma peaks in late adolescence (ages 14 – 17)

Teicher et al., 2016, Nat Neurosci Rev

Does Timing of Trauma Matter? Are there critical sensitive periods?

40Teicher et al., 2016, Nat Rev Neurosci

In those exposed to early life stress or trauma, there appears a peak incidence of trauma exposure in early adolescence (centred around age 10). This unfortunately coincides with a sensitive period of neurobiological vulnerability

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Developmental stages of neural signalling and functional connectivity in prefrontal cortex and limbic structures

41Casey & Jones, 2010, J Am Acad Child Adol Psychiatry

Connectivity between prefrontal cortical regions and limbic regions (amygdala, striatum) increases with age

Risk in adolescence associated with pubertal hormones, predominance of limbic activation and bottom‐up influences on underdeveloped PFC ( the maturational lag between limbic and PFC development)

Changes in amygdala‐PFC connectivity with age

Gabard‐Durnam et al., 2014

Adolescents shown to have impaired fear extinction learning and retention

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Given that fear extinction learning and recall is mediated by VMPFC inhibition onto amygdala, and early adolescence is associated with a predominance of amygdala function relative to PFC – might predict difficulties with fear regulation

Find in rodents and humans that adolescents have significantly impaired fear extinction learning (Pattwell et al., 2012; Casey & Johnson, 2015; Baker et al., 2016)

Less consistent findings for extinction retention

Is exposure therapy going to be as effective for adolescents?

Pattwell et al., 2012, PNAS

Human fMRI Fear Extinction Study in Adolescents and Adults

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Adults displayed better fear extinction recall (lower SCR) and greater DLPFC activity during fear extinction recall than adolescents – all healthy controls.  Given that PTSD is associated with impaired fear extinction recall and DLPFC activity, would predict trauma to exacerbate these patterns

Ganella et al., 2018, Front Human Neurosci

Type and Timing of Trauma Exposure and Impact on PTSD symptoms

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Greatest risk/predictor of PTSD symptoms is the number of types and overall severity of trauma, rather than type of trauma

However, physical neglect and sexual abuse are the types of trauma significantly associated with PTSD symptoms.

Specific age of onset of trauma –peak critical periods for PTSD symptoms at age 5 (and particularly with physical neglect), and a second peak age 12 – 14

(Schalinski & Teicher, 2016, BMC Psychiatry)

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Type and Timing of Trauma and Dissociation symptoms

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Physical and emotional neglect, non‐violent emotional abuse and sexual abuse most significant trauma types associated with dissociation, and duration and number of types of trauma also associated

Peak age of onset for physical neglect impact is 5 but 15 for nonviolent emotional abuse, and 12 for sexual abuse in risk for dissociative symptoms 

Schalinkski & Teicher, 2016, BMC Psychiatry

Type and Timing of Trauma and Depressive Symptoms

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Emotional neglect, sexual abuse and duration of trauma most significantly associated with risk for depressive symptoms.

Emotional neglect around age 10, and sexual abuse around age 12 associated with depressive symptoms

Duration of trauma more important than number of types of trauma or overall severity in depressive symptoms

Schalinski & Teicher, 2016, BMC Psychiatry

Timing of Trauma and Event-Related Potentials to Facial Expressions

Given this evidence of neurobiological and psychological vulnerability during early adolescence, and this clear issue of the potential role of critical sensitive periods interacting with trauma exposure – we are examining this question in the context of affective neural responses (using event-related potentials)

- 137 participants with trauma exposure at different time points

- 21 participants with trauma exposure less than 12 or less (childhood) (M=10 yrs)

- 31 participants with trauma exposure between 13-17 (early adolescence) (M 15)

- 61 participants with trauma exposure between 18-25 (late adolescence) (M 20)

- 24 participants with trauma exposure greater than 25 (adult trauma) (M29)

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Timing of Trauma and Face ERP reponses

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Passive viewing task of blocks of different facial expressions

Angry, Happy, Fearful, Neutral

ERP recorded whilst watching faces

Only reporting from conscious face condition at present

Examined P100 amplitude (early selective attention), and N170 amplitude (amount of face‐specific encoding/processing)

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Timing of Trauma Exposure and P100 amplitude to all facial stimuli

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Significant Group differences of early selective visual attention to emotional faces

Increased P100 amplitude to emotional faces (valence non‐specific) in adults exposed to trauma aged 13‐18 relative to those exposed in adulthood

Amygdala activity has a significant impact on early visual processing of emotional stimuli via amygdala reafferents –P100 amplitude is associated with amygdala function, as patients with amygdala lesions have reduced P100 amp to visual stimuli (Rotshtein et al.., 2010)

*

Timing of Trauma Exposure and P100 amplitude to threatening faces

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Angry Faces

Adults exposed to trauma in early adolescence had significantly greater P100 amp to angry faces than those exposed in childhood (prior to 13 years) who showed blunted P100 amplitude responses

No significant group differences to fearful face expressions

*

Timing of Trauma Exposure and P100 amplitude to Happy Faces

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Happy Faces

Adults exposed to trauma in adolescence displayed significantly greater P100 amplitudes to happy faces than adults *

Timing of Trauma Exposure and P100 amplitude to Neutral Faces

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Adults exposed to trauma in adulthood displayed significantly reduced P100 amplitudes (reflecting early visual attention) to neutral facial expressions compared to all adults exposed to trauma prior to adulthood (childhood, early and late adolescence)

* *

*

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Timing of Trauma Exposure and N170 amplitude to Angry Expressions

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<13              13‐17            18‐25              >25

Significantly reduced N170 amplitude to angry facial expressions in adults exposed to trauma in early adolescence compared to late adolescence and adults

*

*

Timing of Trauma Exposure and N170 amplitude to Fearful Expressions

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<13               13‐17             18‐25            >25

Significantly reduced N170 amplitude to fearful faces in adults exposed to trauma in early and late adolescence compared to those exposed to trauma in adulthood

*

*

Timing of Trauma Exposure and N170 amplitude to Happy Expressions

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* Significantly reduced N170 amplitude to happy faces in group exposed to trauma in early adolescence compared to those exposed in adulthood

<13             13‐17          18‐25          >25

Timing of Trauma Exposure and N170 amplitude to Neutral Faces

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<13             13‐17           18‐25            >25

**

Those exposed to trauma in early adolescence significantly reduced N170 amplitude to neutral faces compared to those exposed in childhood and adulthood

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Conclusions

• Effectively there appears to be something divergent in neural emotional processing in the group who experienced trauma in the critical sensitive early adolescent period

• Interestingly, those exposed to trauma in early adolescence display increased early selective attention to angry and happy faces (and don’t discriminate between them), but they subsequently display reduced later conscious encoding/processing of facial expressions

• This suggests there may be an automatic hypervigilance to all salient stimuli (which is in line with evidence of heightened amygdala reactivity in individuals exposed to trauma in early adolescence), but reduced conscious processing of facial expressions (avoidance?)

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Clinical Implications

• The current study suggests that those individuals exposed in early adolescence have:

• 1) Difficulty discriminating between threat and non-threat signals

• 2) An automatic hypervigilance for salient stimuli

• 3) Reduced later processing of facial expressions

• This might lead to impaired interpersonal functioning, poor risk assessment, and further dysregulation of emotional processing

• Potentially highlights the need for explicit emotion regulation training, and as part of this emotional literacy/awareness training

• Also potentially cognitive bias modifications and risk assessment training

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