PTSD: A Look Inside

 A book slipped through my fingers and hit the floor with a “bang!” Before the echoes stopped, an urgent voice from downstairs demanded, “What happened? Are you OK?” I reassured him and we went about our day. But – and I’m not proud of this – I found myself thinking, It’s been years. Shouldn’t you be over this by now? He wasn’t, and he still isn’t. PTSD may be invisible, but it is deep and can be lasting.

If there is someone in your life who has PTSD, you may also have been through a similar experience. It starts with your own shock and fear from the trauma they suffered. Someone you love was hurt or threatened, perhaps nearly killed. You ache for what happened and can only be grateful it wasn’t worse.

But then, the months (or years) go by, and they are still showing signs of their trauma. They resist going near the scene of their distress, and won’t even talk about it. Their sleep is a battleground. As the experience retreats in time but the reaction goes on and on, you may begin to wonder if their exaggerated fear response is, perhaps… exaggerated. It certainly does not seem healthy. You wonder what is happening to them, and if they will always be that way. You wish you could help, or at least, understand.

The purpose of this article is to explore PTSD through several dimensions: behavioral aspects, what it looks like physically in the brain, and how it traverses through someone’s life. My goal in writing it is to aid understanding of this life-altering illness.

What Is PTSD?

There is a book definition in the Diagnostic and Statistical Manual of Mental Disorders, currently in its fifth edition (DSM-5) that guides U.S. doctors in diagnosing PTSD [1]. According to this source, there are certain elements to look for in making a diagnosis:

• First, there was a traumatic experience: an exposure to actual or threatened death, serious injury, or sexual violence. It could have been experienced first-hand, or witnessed, or it could be something that you hear about happening to a loved one. There’s even room in the definition for something like a fireman having to go pick up human body parts after a terrible accident.

• Next, there is the mental response, like recurrent, distressing, and intrusive memories of the event. The patient closes his or her eyes, and they are back there. They could be doing something entirely unrelated to the event – shopping, or walking the dog – and the memory just pops back in their head. It invades their dreams, or they suddenly feel like they are back at the scene of the trauma, and that it is happening again. Given a cue – some similar aspects of the trauma (like the “bang” from that book hitting the floor) they are right back where it happened, in their mind. They break out in a sweat; their heart races – just like when it happened for real. And they can’t control those memories or feelings.

• So, they take steps to avoid those experiences. Mentally and physically, they stay away from anything that might remind them of the trauma.

• And then the negativity piles on. Their memory of the event may be affected so that there are aspects of it that they can’t recall. Their whole outlook on life may be colored with negativity – they feel worthless; the world is a bad place; and on and on. They feel detached from reality, or worse, instead of positive emotions, they can only experience negative ones: sadness, guilt, hopelessness.

• And then there’s the behavioral changes, so apparent to those of us who are on the outside: irritability, hypervigilance, outbursts of anger, sleep disturbance, inability to focus or concentrate.

The DSM is a guide, though, not a checklist. Someone doesn’t have to hit every symptom to be diagnosed with PTSD. There are different levels of severity, also, and differing degrees to which the symptoms, put together, negatively impact someone’s life. That’s an important aspect to any disorder –a “disorder” is a combination of symptoms severe enough to disrupt some important aspect of the patient’s life. It could pose a problem with their job, or in getting employment; it could create problems in their family life or social life, or impede other areas of functioning. It’s generally bad enough that the patient seeks treatment, or his or her family seeks it on their behalf.

So that’s the book definition. And, because the DSM is also a statistical manual, it includes the tidbit that about 9 percent of the U.S. population will meet the criteria for diagnosis sometime in their lifetime; about 3.5 percent in any year. Those numbers are heavily weighted toward survivors of rape, military combat, terrorist attack, and genocide or mass incarceration, who suffer at a rate of about 37 percent [2].

In 2013, a research team analyzing the results of 35 different studies of PTSD found that the disorder generally had a different course when it resulted from intentionally-inflicted harm (e.g., terrorist attack or rape) than when resulting from unintentional harm (e.g. natural disaster or plane crash). In the former cases, the possibility of developing PTSD increased over the first year following the trauma: about 12 percent of those who directly experienced intentional harm had developed PTSD at 1 month, growing to 23 percent at 12 months. For those subjected to unintentional harm, the prevalence of the disorder went the other way: about 30 percent had developed PTSD at 1 month, declining to 14 percent at 12 months. For about a third of those who developed PTSD after being subjected to intentional harm, the disorder went away on its own in a few months. For another 40 percent, though, their PTSD was still running strong even a year later [2].

Under The Hood

(This part is going to get technical, but there’s a reason for that: it is to challenge the stigma of mental illness. When you see the physical processes behind a psychiatric illness, it is easier to think of it in medical terms – similar to a stroke or concussion – rather than in stigmatizing terms: as a weakness, choice, or errors in thought patterns. Or as demonic possession, or “just plum crazy.” There are reasons for the behavioral changes that characterize psychiatric illnesses.)

Using modern technology, scientists can visualize much of what is actually happening inside the brain of a living person at a very granular level. So far, PTSD imaging studies have provided some useful clues about what underlies the illness, though they haven’t been able to point to a smoking gun (please pardon the reference to violence). Still, what they reveal about PTSD helps point the way toward its origins and actions, giving us hope that someday we may be able to predict it, prevent it, treat it, and even cure it. Generally, these studies address what the brain of someone with PTSD does that is different than the brain of someone without (functional imaging), or physical differences in the brain of someone with PTSD versus someone without (structural imaging).

Starting with functional imaging, someone with PTSD might find his heart pounding and nerves on end in response to what used to be ordinary daily encounters – a noise, a look, a smell. Those physical responses start in the brain, and it shouldn’t come as a surprise that someone with PTSD experiences stronger activation of brain circuits involved in emotional processing and control, compared to someone without (including people who suffered trauma but did not develop PTSD and healthy controls with no trauma exposure). Or that those emotions echo most strongly on the negative side – typically, a persistent, unwarranted but unshakeable sense of threat [3].

There are several areas of the brain involved with emotional processing and control that show greater-than-normal activation in PTSD: the amygdala, hippocampus, insula, anterior cingulate cortex, and the ventromedial prefrontal cortex. Combined, activation patterns in these regions indicate that someone with PTSD is more attentive to negative images and less able to disengage from them, compared to someone without the disorder.

Multiple functional imaging studies highlight the amygdala and hippocampus as being very strongly activated in PTSD. (Those structures, as well as the insula, exist on both sides of the brain. Though I refer to them like singular structures, we each have two of them: a left and a right.) The amygdala is a key part of the brain’s emotion-processing circuit. Though commonly called the “fear center” of the brain, the amygdala is actually responsible for evaluating the emotional significance of our perceptions. It responds to positive perceptions (like seeing a happy expression on a face); however, it earned its reputation by being more likely to label perceptions with negative values like fear, anger, or sadness. Studies repeatedly show that people with PTSD experience a higher degree of activation of the amygdala – corresponding to feelings of fear, anger, and sadness – when compared to people without the disorder [3].

The hippocampus is also involved in emotional processing and in PTSD. It is essential to learning and memory: putting recent memories into longer-term storage, and rebuilding them later. In cases of PTSD, it is more strongly activated in processing negative memory cues than the same region in people without PTSD, and, at the same time, less strongly activated in response to positive cues [3].

Though all these brain structures show unusually high activity levels in PTSD, the hippocampus is the only one of them that reliably shows structural differences in people with PTSD versus someone without. And, that may be a pre-existing condition – a risk factor for the illness – rather than something caused by the illness.

Magnetic resonance imaging (MRI) can measure the size and shape of even very small structures in the brain. A 2018 study that combined MRI results from almost 800 people with PTSD found that they had smaller hippocampus structures than did the more than 1,000 comparison subjects (people who were exposed to similar traumas but didn’t develop PTSD, or healthy control subjects with no such exposure). Further, the smaller the hippocampus, the more severe the PTSD. The researchers also compared other parts of the brain of the PTSD group to the non-PTSD group (like the amygdala), but did not find a statistically-significant difference in any of those other structures. [4]

This finding has to be taken in context, though. A 2002 MRI study of Vietnam veterans indicated that smaller hippocampus volume may be a pre-existing condition that makes people more vulnerable to developing PTSD. That study involved 40 pairs of identical twins, all male, in which one twin had served in combat in Vietnam and the other twin had not. In 17 of the twin-pairs, the combat-exposed twin got PTSD. Across those 17 cases, both the PTSD twin and the non-exposed, non-PTSD twin had a smaller hippocampus when compared to the other 23 twin pairs [5]. The comparatively smaller hippocampus in those 17 combat veterans with PTSD was genetic – their identical twins also had smaller hippocampus. It pre-existed their PTSD rather than resulting from it.

The brain is constantly adapting: forming new connections and trimming away lightly-used ones. Even entire brain cells and parts of cells are created or destroyed over the lifetime. These processes are particularly relevant to the hippocampus, which is the brain’s key structure for memory consolidation and retrieval. The hippocampus specializes in storing memories away and rebuilding them later from storage. It also plays an important role in fear extinction – a positive process in which new, benign memories involving similar (but not traumatic) situations eventually overwhelm the older, frightening ones. Shedding bad memories or persistent fears involves more than some connections fading away. PTSD is thought to involve these processes closely: memories tagged with seriously negative emotional content are constantly recalled, while the fear extinction mechanism fails. [4, 6]

Over the years, scientific research has discovered other ways in which people with PTSD differ from people without PTSD, including evidence of a higher level of inflammation in the brain [7], differences in the stress cycle [8], and reduced signaling of GABA (a neurotransmitter that tends to dampen down brain activity) in some parts of the brain [9]. So far, though, none of this research has identified a definitive cause of PTSD. It has, however, suggested some candidate drugs for treating it: anti-inflammatories, hydrocortisone (which impacts the stress cycle), and anti-anxiety medications (which target inhibitory connections among brain cells).

There is still so much to learn about PTSD, but what is known even now provides hope for its survivors. So, let’s look next at what doctors are doing to treat PTSD. What works in the real world?

References:

[1] American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders, 5th ed. (DSM-5). Arlington: American Psychiatric Association, pg. 271-280.

[2] Santiago PN, Ursano RJ, Gray CL, Pynoos RS, Spiegel D, et al. (2013) A Systematic Review of PTSD Prevalence and Trajectories in DSM-5 Defined Trauma Exposed Populations: Intentional and Non-Intentional Traumatic Events. PLoS ONE 8(4): e59236.

[3] Fitzgerald, J. M., DiGangi, J. A., & Phan, K. L. (2018). Functional neuroanatomy of emotion and its regulation in PTSD. Harvard review of psychiatry, 26(3), 116.

[4] Logue, M. W., van Rooij, S. J., Dennis, E. L., Davis, S. L., Hayes, J. P., Stevens, J. S., ... & Morey, R. A. (2018). Smaller hippocampal volume in posttraumatic stress disorder: a multisite ENIGMA-PGC study: subcortical volumetry results from posttraumatic stress disorder consortia. Biological psychiatry, 83(3), 244-253.

[5] Gilbertson, M. W., Shenton, M. E., Ciszewski, A., Kasai, K., Lasko, N. B., Orr, S. P., & Pitman, R. K. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature neuroscience, 5(11), 1242-1247.

[6] Zuj, D. V., Palmer, M. A., Lommen, M. J. J., & Felmingham, K. L. (2016). The centrality of fear extinction in linking risk factors to PTSD: A narrative review. Neuroscience and Biobehavioral Reviews, 69, 15-35.

[7] Friend SF, Nachnani R, Powell SB, Risbrough VB. (2022). C-Reactive Protein: Marker of risk for post-traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery. Eur J Neurosci. 55(9):2297–2310.

[8] Dunlop, B. W., & Wong, A. (2019). The hypothalamic-pituitary-adrenal axis in PTSD: Pathophysiology and treatment interventions. Progress in Neuro-psychopharmacology and biological psychiatry, 89, 361-379.

[9] Garfinkel, S. N., & Liberzon, I. (2009). Neurobiology of PTSD: A review of neuroimaging findings. Psychiatric Annals, 39(6).