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. Treatments to target structural changes are examined for effectiveness.

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). The government itself spends around $6.2 billion on

PTSD and depression within military troops according to a 2008 study. For a disorder so

prevalent, scientists and society as a whole know too little about it. Education is key to making

advancements with this disorder. PTSD was first defined in the third edition of the Diagnostic

and Statistical Manual of Mental Disorders, or the DSM-III, in 1980. Since then research has

developed to better understand the key concept of trauma, and how an external stressor is filtered
 Neurobiology of PTSD 3

through cognitive and emotional processes to produce a different effect in every individual

(Friedman, 2016) . PTSD as most currently 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 paper is to define the structural alterations in the brain that are the basis of these

detrimental symptoms, and find connections with treatments that target these alterations.

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). 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 of those with PTSD lie in the

hyperactivated amygdala, decreases hippocampal volume, and thinner prefrontal cortex. These

alterations translate, in order, to hyperarousal, failures in working memory, attention, and

 Neurobiology of PTSD 4

cognitive flexibility, and increased numbing and avoidance of affected patients. Cognitive

Behavioral Therapy has been found to target both the amygdala and areas in the brain related to

empathy and forgiveness.

Manifestation of PTSD Symptoms

Before understanding the biology behind the symptoms of PTSD, it is integral to

understand the symptoms themselves. Examining the first category of re-experiencing embodies

emotionally or perceptually reliving traumatic events either spontaneously or in response to

triggers. This can be seen through distressing recollections or dreams of the event, as well as

illusions, hallucinations, or flashbacks either when awake or intoxicated. When exposed to cues

that in any way resemble the trauma, strong psychological distress or physiological responses

may be present (Koek et al., 2014). The wife of a Vietnam War veteran gave an anecdote about

her family trip to the amusement park in a TedTalk that explained this category of symptoms

well. Upon riding the giant rocking boat ride, her husband had an anxiety attack and threw up

afterwards because the rocking motion sent him into a flashback of a time when he was thrown

from a helicopter and covered in other soldiers blood (Seahorn, 2016). The next category of

avoidance and numbing refers to an increase in social isolation and attempted efforts to avoid

any thoughts, conversations, places, people, or activities that could remind of trauma. Other

symptoms may be an inability to remember pieces of the trauma, loss of interest in participating

in usual activities, and a sense of a shortened future without a career, children, etc. The category

of hyperarousal is the most obvious to spot for people close to those affected by PTSD,

especially family members. It is characterized by difficulty falling or staying asleep, difficulty

concentrating, and increased irritability or outbursts of anger (Koek et al., 2014). The same
 Neurobiology of PTSD 5

veteran who had the flashback on the rollercoaster would also become uncharacteristically angry

when his family would a couple minutes late to leave the house. After one minute, he would start

to pace. After two minutes, he would start to get very anxious. And after three, he would be

yelling at them to get going. This uncalled for anger is also a part of the hypervigilance or high

intensity of behavior that falls under the hyperarousal category. This high sensitivity comes with

the purpose of detecting threats, and in the case with the veteran, being just one or two minutes

late could mean the death of many other soldiers (Seahorn, 2016). The other common symptom

within hyperarousal is an exaggerated startle response to everyday occurrences. For example,

fireworks on the Fourth of July could immediately cause a veteran to drop to the ground in cover

because it reminds them of gun fire (Rigg, 2015). The final category of negative alterations in

cognitions and mood refers to persistent and distorted negative beliefs or blame of oneself,

others, or the world. Soldiers may have persistent negative emotions related to trauma such as

fear, guilt, or anger, and an inability to experience positive emotions in general (Koek et al.,

2014). It is necessary to understand these symptoms in order to pick up on the signs that

someone might be experiencing Post Traumatic Stress Disorder; but, how do all these symptoms

occur? It is known that PTSD is an invisible wound because it manifests itself silently into the

body, but where? The most basic beginnings to the problem comes from the response to fear.

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).
 Neurobiology of PTSD 6

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 communicates with the subcortical parts of the hippocampus and the

hypothalamus which secretes corticotropin, a hormone that activates the pituitary gland. This

gland secretes an adrenocorticotropic hormone whose job is to activate the adrenal gland to

increase 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 that uses the

subcortical brain passages. The problem occurs upon returning home, when 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

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 - the

parts of the brain related to the fear circuit described above (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
 Neurobiology of PTSD 7

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 or bottom portion of the

structure (Mazza, Tempesta, Pino, Catalucci, Gallucci, Ferrara, 2013; Bremner, 2006; Shin et al.,

1997; Eckart et al., 2011). Different pieces of the amygdala have different specializations, and

the basal part of the amygdala is a part of the basolateral complex that is primarily in charge of

stimulating the fear response that is heightened in those with PTSD (Basolateral Amygdala,

2017). Structurally, dendritic hypertrophy, or overgrowth of the branched extensions at the end

of nerve cells that receive stimuli, occurs (Kolassa & Elbert, 2007). The prefrontal cortex, or

PFC, 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). When trauma-related

memories are triggered, Brocas area experiences hypoperfusion, which is a decreased and

insufficient blood flow to that area of the brain, causing low oxygen and death of brain tissue. In

other words, that area in charge of labelling emotions is deactivated in the presence of something

related to the trauma experienced (Hull, 2002). In one study, patients viewed negative

emotional valence images which are images that trigger an averse emotional response, 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
 Neurobiology of PTSD 8

structures, though they cannot encompass the entirety of the complex disorder, are the most

noted in studies of neurobiology. A fascinating addition to this understanding of brain structure

is the idea of a building block effect. The volume loss or over activity supposedly correlates to

the extent of traumatization (Eckart et al., 2011). This phenomenon supports the findings that the

more experiences with trauma one encounters, the greater their risk of getting PTSD. Still, there

is no way of defining or placing traumas into categories that draw the line between what will

cause PTSD and what will not. Interestingly, looking forward studies have found the brains

plasticity to allow reversibility of structural changes in the hippocampus and medial prefrontal

cortex but not the hypertrophy in the amygdala (Kolassa & Elbert, 2007). This lack of plasticity

could be a reason why symptoms take a very long time, and sometimes never go away. The brain

is what keeps the body regulated and functioning, so when noticeable and large changes appear,

there is no reason to doubt that there will be changes in the functioning of the human being as a

result. In the case of PTSD, most of these major structures affected link to either memory and

cognition or the primitive, subcortical brain in charge of responding to stimuli such as fear.

Therefore, the symptoms experienced by soldiers or others with PTSD fall back to the parts

involved in these processes.

Hypothesized Structure Changes

Comparing the major changes in the brain to the amount and complexity of symptoms, it

becomes clear that there is no way the changes listed above could suffice for the entire

explanation of the disorder. Eckart et al. in 2001 tentatively found additional parts of the cortex

that would be included in the emotional processing network. These structures included reduced

brain volumes in lateral prefrontal regions, the right inferior parietal cortex, and the bilateral
 Neurobiology of PTSD 9

isthmus of the cingulate. These changes could explain memory disturbances, fragmentation of

traumatic memories, worse autobiographical memories, or high occurrence of recurrent, intrusive

recollection of traumatic memories (Eckart et al., 2011). Another study linked the left medial

temporal gyrus to capacity for empathy, and the posterior cingulate gyrus the capacity for

forgiveness, both of which had lower activation in patients with PTSD (Porto et al., 2009). It was

mentioned early that trauma could not be categorized because it is unique to the individual who

experienced it. One of the reasons that so much in this field is hypothesized, or not completely

certain, is because it is incredibly difficult to study neuroimaging from such personalized

responses. Neuroimaging, or looking at structures or activity in the brain, is a new research

method itself, beginning in 2001. A problem in the general study of trauma is the specific and

typically homogeneous population researched. It was noted by one study that a majority of

reports on the neurobiology of PTSD were taken from combat veterans, a majority male (Hull,

2002). Even though that study was done in 2002, homogeneity was obvious as a majority of the

studies in this paper are from a population of war veterans. In the future, it is important to

incorporate a wider group of trauma to find and validate results.

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.,
 Neurobiology of PTSD 10

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). Finally, the Brocas area

that deactivates in the presence of trauma-stimuli explains why patients with PTSD experience

very strong emotions without being able to understand them, or put their experience into words

(Hull, 2002).

Treatment Implications

If researchers can find the specific malfunctions within the brain, and which symptoms

they connect to, then the most important place to go from there is determining effective

treatments. One psychological treatment that appears ineffective is talk therapy due to the

disorder within Brocas area that makes understanding the trauma through words difficult (Hull,

2002). Cognitive Behavior Therapy, commonly known as CBT, has been found to effectively

target the hippocampus. One study in 2013 found that by the end of treatment, no apparent

differences could be found in the size of the hippocampus between subjects with or without

PTSD (Levy-Gigi et al.). However, the hippocampus lends itself to healing because it is unique
 Neurobiology of PTSD 11

in its ability to regenerate neurons (Gould et al , 1998). CBT also led to an increase in activation

of both of the structures related to empathy and forgiveness listed previously (Porto et al., 2009).

Finally, the amygdala was said to be the least plastic earlier, but researchers are considering as

early as 2014, the positive and negative effects of deep brain stimulation (DBS) of the amygdala

in the case that other treatments have failed to be effective for a patient. As mentioned before,

neuroimaging studies have found the amygdala to be the source of hyperarousal, and DBS of the

basolateral nucleus could produce an improvement in both function and symptoms. The main

drawbacks are risks that come with any neurological procedure, as well as risks with long-term

electric stimulation in deep brain tissue (Koek et al., 2014).

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 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 some symptoms such as hyperarousal have a direct link to the amygdala, not all

symptoms can be paired with a specific brain structure. 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 of

those with PTSD lie in the hyperactivated amygdala, decreases hippocampal volume, and thinner

prefrontal cortex. These alterations translate, in order, to hyperarousal, failures in working

memory, attention, and cognitive flexibility, and increased numbing and avoidance of affected
 Neurobiology of PTSD 12

patients. There are several other hypothesized areas of change that much be researched further to

be validated, but PTSD is a disorder that is increasingly being studied because of its complexity.

Treatments have begun to explore the brain-behavior connection as well, and Cognitive

Behavioral Therapy has proven effective in reversing certain structural problems in the

hippocampus, though we do not know the effect on behavior this causes. It also alleviated

functioning problems in the areas that deal with empathy and forgiveness which would fall under

either the emotional numbing or negative alterations in cognition and mood category of

symptoms.
 Neurobiology of PTSD 13

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