Neurobiology of PTSD 1

Running Head: NEUROBIOLOGY OF PTSD

Neurobiology and Behavioral Responses of P.T.S.D.

Sarah Concepcion

Glen Allen High School

 Neurobiology of PTSD 2

Abstract

This review discusses the most current research regarding the structural alterations in the

brain as a result of Post Traumatic Stress Disorder, and how those affect the symptoms or behaviors

of the individuals. The first part of the review describes the basic neurobiology of fear and stress,

providing a sequential process for how the brain interprets outside stimuli. Second, the three main

alterations in the brain are discussed to show the backwards processing of information in PTSD

patients. Brain plasticity of each structure is mentioned. Following is an exploration of the effects

these structural changes have on behavior. The conclusion suggests a final answer yet pushes for

further research to resolve discrepancies or gaps left in the brain-behavior link.

Introduction

Approximately 5 to 10 percent of the adult population has experienced Post Traumatic

Stress Disorder at some point in their lives (Bremner, 2006; Koek et al., 2014). The prevalence of

PTSD cases in the past years has increased as the population of veterans returning from Iraq and

Afghanistan have been seeking help. Between 15 and 20 percent of military personnel are affected

by PTSD, with approximately a 14 percent prevalence in Operation Iraqi and Enduring Freedom

veterans only (Koek et al., 2014). PTSD as defined by the DSM V is the occurrence of distressing

or disabling perceptual, emotional, and behavioral changes that persist after an experience in which

the sufferer has witnessed or been threatened with death or severe injury (Koek et al., 2014). In a

simpler, biologically tailored definition, PTSD is a reordering of neural networks and sensory

pathways designed for a person to survive a dangerous situation (Seahorn, 2016). The main

symptoms are clustered into four groups: re-experiencing of traumatic event, avoidance and

emotional numbing, hyperarousal, and negative alterations in cognition and mood, with specific

symptoms falling into such categories (Koek et al., 2014). The purpose of this literature review is to
 Neurobiology of PTSD 3

define the structural alterations in the brain that are the basis of these detrimental symptoms.

Studying neurobiology behind PTSD benefits scientists and clinicians through finding connections

between symptom presentations and potential neurobiological markers that could assist in finding

effective treatments (Wrocklage et al., 2017).

Normal Biological Response to Fear

The human brain has two distinctive parts separated into the cortical and subcortical brain.

The cortices of the brain receive sensory information, processes it, and make decisions that

influence personality and individuality. The subcortical brain is the primitive brain in charge of

uncontrollable instincts and basic needs such as food, sex, and overall survival (Rigg, 2015). When

a stress related threat occurs, the sensory information is relayed through the thalamus to both the

cortex, more specifically the sensory and association areas and prefrontal, and the amygdala

(Taylor, 2006). The cortex, the slower processing system, then sends stimulus processing and

inhibition of fear from the medial prefrontal cortex to the amygdala (Kolassa & Elbert, 2007).

However, since the pathway between thalamus and amygdala is faster, in the meantime, the

amygdala has been communicating with the subcortical parts of the hippocampus and the

hypothalamus which secretes corticotropin to activate the pituitary gland. This gland secretes an

adrenocorticotropic hormone to activate the adrenal gland which increases arousal while the body

decides whether to fight, flee, or be stuck in tonic immobility (Taylor, 2006). When soldiers are

deployed, they are placed in a situation where the enemy wants to kill them, so they are in this

constant fight or flight survival instinct. Upon returning home, the cortices understand the

geographic shift back to US, but the survival mode of the limbic system does not register it, keeping

the body in a constant fear state (Rigg, 2015).

Main Structural Changes

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When under that constant stress, it is not surprising that the brain parts relating to the fear

circuitry end up damaged. The main disturbances from PTSD have been found in the functioning of

the neural network located in the medial prefrontal and medial temporal lobe structures (Eckart et

al., 2011). The hippocampus and hypothalamic-pituitary-adrenal axis (HPA) which are involved in

the feedback regulation of the stress hormone cortisol are found to be smaller in PTSD patients

since long term stress causes decreased formation of new nerve cells in the dentate gyrus (a

subregion of the hippocampus), decreased hippocampal cell survival, and increased programmed

cell death (Bremner 2006; Kolassa & Elbert, 2007). Multiple studies have found the amygdala to by

hyperactivated, or overactive, especially concentrated in the basal portion of the structure (Mazza,

Tempesta, Pino, Catalucci, Gallucci, Ferrara, 2013; Bremner, 2006; Shin et al., 1997; Eckart et al.,

2011). Structurally, dendritic hypertrophy or overgrowth of the branched extensions of a nerve cells

occurs (Kolassa & Elbert, 2007). The prefrontal cortex as a whole is found to be thinner in those

with PTSD than those without. The ventrolateral (underside) and dorsolateral (upper side) PFC, as

well as left dorsal ACC or anterior cingulate cortex, have showed significant reductions with an

increase in symptom severity of PTSD due to the atrophy of dendrites (Kolassa & Elbert, 2007;

Wrocklage et al., 2017). In one study, patients viewed negative emotional valence images and

researchers found that subjects with PTSD had higher reactivity in the amygdala and less response

in the prefrontal and frontal cortex. When you combine these two it suggests an immediate reaction

to emotional stimuli (subcortical brain) without more complex information processing (cortical

brain) as mentioned in the previous section (Mazza et al., 2013). These three structures, though they

cannot encompass the entirety of the complex disorder, are the most noted in studies of

neurobiology. Interestingly, studies have found the brains plasticity to allow reversibility of
 Neurobiology of PTSD 5

structural changes in the hippocampus and medial prefrontal cortex but not the hypertrophy in the

amygdala (Kolassa & Elbert, 2007).

Impact on Behavior

Hyperarousal, or symptoms under this category which include irritability, aggression,

nightmares, and insomnia, are caused at least in part caused by the overactive amygdala (Koek et

al., 2014; The Circuitry of Fear, 2013). Intrusive memories and hyperarousal are consistent with

either a more responsive amygdala and a less active medial PFC (Kolassa & Elbert, 2007). In

regards to memory, the loss of dendrites and spines in pyramidal cells of the prefrontal cortex

correspond to failures in working memory, attention, and cognitive flexibility (Wrocklage et al.,

2017). To connect the two, when hyperarousal occurs, the cortisol itself that is released inhibits

memory (Rigg, 2015).

Decreased activity in the cortexes could possibly be the underlying cause of avoidance and

numbing symptoms (Mazza et al., 2013). Since the prefrontal cortex recognizes emotions, increases

self-awareness, and controls the experience of pleasure, problems surrounding it can result in

insensitivity or withdrawal from important relationships and social settings (Bremner, 2006; Rigg,

2015; Eckart et al., 2011). A study examining cortical thickness found that it negatively correlated

with symptom severity in brain regions relevant to emotional inhibition and emotion-cognition

interactions. More specifically, the dorsal ACC was associated with numbing, but not arousal or

reexperiencing (Wrocklage et al., 2017).

Conclusion

The research linking the behavioral and biological connections uncovers both the

intertwining of functions of the brain and the uncertainty of specific brain-behavior links. The

overuse of the subcortical brain in PTSD is clear from the main alterations in the brain that create a
 Neurobiology of PTSD 6

constant fear circuitry or response to stimuli that may not be harmful in the slightest way. Though

this is proven, researchers are currently unclear about all of the brains effects on the symptoms.

While categories such as emotional numbing and hyperarousal have more validated connections with

brain alterations, symptom categories such as reexperiencing and negative alterations in cognition

and mood and the structure of the hippocampus do not have strong claims in regard to their linkage.

Furthermore, not all complex symptoms can be attributed to solely three parts of the brain, so further

research is advised to find less common but still significant alteration in the brain. Despite this, the

main structural alterations in the brain lie in the hyperactivated amygdala, decreases hippocampal

volume, and thinner prefrontal cortex. These alterations translate to hyperarousal, failures in working

memory, attention, and cognitive flexibility, and increased numbing and avoidance.

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