The Neural Nuances Underlying Post-Traumatic Stress Disorder (PTSD) (by Danielle Steinbach)

The slamming of a door as loud and sudden as a gunshot. 

The fall of angry footsteps on a wooden floor. 

The clang of an alarm bell. 

All of these are events that can easily trigger an episode of post-traumatic stress disorder (PTSD). A psychological condition that occurs in response to terrifying life experiences, PTSD infringes on every aspect of someone’s life, impacting someone on a physical, mental, and social level. Symptoms include flashbacks, insomnia, bouts of panic, apathy, social isolation, irritability, a rapid pulse, low self-esteem, and uncontrollable, sudden recollections of the initial trauma. 

Although history is riddled with a series of wars and traumas, PTSD was only first officially recognized in the Diagnostic and Statistic Manual of Mental Health Disorders (DSM) in 1980. However, true observations of PTSD have been recorded long before then. 

As soldiers returned home from World War I, physicians and family members began noticing marked changes in behavior. Beyond a heightened fear response to loud sounds, some soldiers would experience debilitating shaking, fainting, and even an inability to speak. 

As these symptoms recurred in soldiers returning from World War II, the Korean War, and the Vietnam War, psychologists and cognitive scientists began investigating this condition more closely, questioning where exactly in the brain changes occur after traumatic life events. 

This investigation led researchers to identify a key network of brain regions involved in the chronic fear response seen in PTSD. 

The Hippocampus 

When questioning how memories of life events affect us years into the future, the first brain region to consider is the hippocampus. Responsible for the initial encoding of memories to long-term storage in the brain, the hippocampus processes our lives as a story that gets ingrained and distributed throughout the processing regions of the cerebral cortex. 

And this is the crux of the troubles of PTSD: recurring and unwanted memories.  

As we proceed through life, we rely on our store of memories and prior experiences to better understand what is happening in the present. The hippocampus largely coordinates this process of retrieving memories when deciding how to respond to something currently happening. However, while the hippocampus can allow you to compare past experiences to current ones, it also performs the critical role of distinguishing between the past and the present. 

For example, when navigating the school halls to reach their class, a student will recall previous times that they walked those halls to find that classroom; however, the brain will still recognize that these are two separate events in which the student is walking to class, even though they are very similar experiences. 

In PTSD, the ability of the hippocampus to distinguish between past experiences and current life becomes diminished, leading to a blurring of prior experiences and the present. It is for this reason that a veteran may jump upon hearing the punctuated drilling of construction and believe for a petrifying moment that they are under open fire again in the war arena. 

The startling sounds of construction are deemed similar enough to the clamorous sounds of war that the hippocampus retrieves the memory of war as a ‘reference point’ to perceive and understand what the sounds of construction could be. Essentially, the hippocampus over-associates harmless sensations (from sights to sounds to touches) in the present with dangerous memories of the past and continues drawing up those painful experiences to the forefront of the mind – this explains the symptom of recurring thoughts of traumatic experiences.

In addition to this functional abnormality, patients with PTSD also exhibit structural changes, namely a shrinking of the hippocampus. These structural changes could result in a distortion of past memories such that one recalls aspects of traumatic experiences differently and more frequently than others. In fact, studies suggest that being born with a smaller hippocampus could predispose someone to PTSD, although the link between hippocampal changes and PTSD is yet to be fully characterized.  

The Amygdala and the Hypothalamic-Pituitary-Adrenal (HPA) Axis

Next on the list of target regions to be studied in PTSD is the amygdala: the fear hub and a vital player in the limbic system. Working in concert with the hippocampus, the amygdala enables the initiation of both an emotional and physiological fear response in the body. 

Overactive negative memory retrieval triggers overaction of the amygdala, leading to a chronic state of anxiety and, in some cases, panic attacks. When confronted with stimuli that vaguely resemble traumatic experiences, the amygdala initiates the release of corticotropin-releasing hormone from the hypothalamus, which induces the pituitary to send adrenocorticotropic hormone into the bloodstream. This chemical signal will circulate throughout the body until it reaches its final target, the adrenal glands. One adrenocorticotropic hormone binds to receptors on the adrenal glands, the stress hormone cortisol spikes in the body. 

With PTSD, this stress circuit gets repeatedly stimulated, placing the body under a crushing and wearying state of long-term stress. 

The Prefrontal Cortex 

One of the most prominent symptoms of PTSD can be the associated behavioral and personality changes. Loved ones of those with PTSD often report observing mood swings or apathy towards life. These changes stem from observed functional changes in the prefrontal cortex, a region of the brain particularly developed in humans compared to all other species due to its significance in logical reasoning, social interaction, and personality. Symptoms such as mood swings, apathy, and decreased self-inhibition suggest a dysregulation of neurotransmitters in the prefrontal cortex with PTSD.  

Chemical Imbalance 

When examining diseases of the brain, it is critical to recall that the brain operates on multiple levels, from the molecular to the electrical to the chemical. In response to severely traumatic events, the brain will respond to heightened stress by altering chemical production. 

One of the most significant neurotransmitters correlated with PTSD incidence is neuropeptide Y (NPY), which exists largely in structures within the limbic and reward systems, including the nucleus accumbens, the amygdala, and the hypothalamus. In order to compare NPY levels between healthy controls and patients with PTSD, researchers extracted samples of cerebrospinal fluid (CSF) from study subjects. As a reminder, CSF is the clear fluid that circulates throughout the brain to cushion the brain against impact and clear out toxins as well as metabolic byproducts from the brain. From these CSF extractions, researchers discovered that those with PTSD often exhibited deficiencies of NPY. By acting in the amygdala, NPY serves to balance out the fear and anxiety response. Thus, dysregulation of NPY suggests a mechanism for the chronic stress response characteristic of PTSD. 

Considering anxiety regulation, patients with PTSD exhibit heightened levels of “stress-response” activating chemicals, such as norepinephrine and glucocorticoids. However, heightened levels of these stress hormones are a symptom, rather than a cause, of a deeper dysfunction in the limbic system that occurs after trauma. Altered levels of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) could also contribute to a lack of suppression of the stress response, with the mind never allowing itself to shift to a state of rest. 

Takeaways 

As with many psychological conditions, PTSD is a condition that arises from many factors, including structural neural changes, chemical imbalances, and environment. However, as researchers discover more about the nuances of the mechanisms driving this condition, more opportunities arise for us to increase the precision of treatment plans for afflicted patients.

– Danielle Steinbach 

Sources: 

https://www.hhrlaw.com/blog/2018/february/the-first-known-case-of-ptsd/

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