Heritability of Post Traumatic Stress Disorder 

Throughout the past two centuries, literature surrounding psychiatric disorders has developed significantly, specifically in the case of Post-Traumatic Stress Disorder or PTSD. The disorder, only formally addressed within the American Psychiatric Associations’ 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1980, has a background within the American psychiatric community which is fraught with political motivation and ambiguity due to its association with the U.S. Army, as well as women’s rights throughout the 19th and 20th centuries.

As the first edition of the DSM was published post-World War II in 1952, many were searching for way to define the disorders arising within different groups after the war, including Holocaust survivors as well as soldiers. When the DSM-III finally included the diagnosis of PTSD, many believed they had finally found an answer.

The initial diagnosis of PTSD had four criteria:

1. the existence of a recognizable stressor that would evoke distress in nearly anyone;
2. at least one of three types of reexperiencing symptoms (recurrent and intrusive recollections, recurrent dreams, or suddenly acting as if the traumatic event were recurring);
3. at least one indicator of numbing of responsiveness or reduced involvement in the world (diminished interest in activities, feeling of detachment and disinterest, or conflicted affect); and
4. at least two of an array of other symptoms, including hyperarousal or startle, sleep disturbance, survivor guilt, memory impairment, or trouble concentrating, avoidance of activities reminiscent of the trauma, or intensification of symptoms when exposed to reminiscent events.

   (American Psychiatric Association, 1980).

Yet, this diagnosis was met with controversy as many believed the disorder had been constructed for “litigious rather than a clinical purpose” (Friedman et al.

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, 2010). For example, the DSM-III claimed that a traumatic evet was one which occurred “beyond the range of normal human experience”, a term which allowed many to disqualify household abuse.

With the introduction of the DSM-IV, Acute Stress Disorder or ASD was introduced. ASD allowed for a diagnosis within 1 month of the traumatic event before PTSD was able to be diagnosed (American Psychiatric Association, 1994, 2000). Additionally, it was determined that PTSD is a “dose-response relationship”, meaning it develops in correlation to the severity of the exposure trauma. For example, in the U.S. where 50-60% of people are exposed to trauma within their lifetime, only 7.8% are diagnosed with PTSD, while in Algeria where 92% of people are exposed to trauma within their lifetime, 37.4% are diagnosed with PTSD (de Jong et al., 2001). It has also been found that the development of PTSD differs based on the source of the trauma. In the United States, for example, trauma in females involving abuse results in much more frequent subsequent PTSD diagnosis than trauma in females resulting from an accident (Kessler et al., 1995).

The most recent manual of psychiatric disorders, the DSM-V published in 2013, introduced within the criterion of stressor the idea that a trauma does not need to be experienced first-hand in order to result in PTSD. The DSM states that stressor could be experienced “indirectly, by learning that a close relative or close friend was exposed to trauma” or through “repeated or extreme indirect to aversive details of the event(s), usually in the course of professional duties” (American Psychiatric Association, 2013). This differs greatly from the original definition within the DSM-III in which the trauma needed to have been “beyond the range of normal human experience”. Now, even if one’s job as a first responder or child abuse lawyer caused one to be exposed to these traumas daily and it is ‘normal’, one could be diagnosed with PTSD.

This new criterion opened up a question of PTSD which has long been debated: can PTSD be passed on from one who experienced a trauma (the parent) to one who had not (the offspring), such as the offspring of Holocaust survivors or army veterans. This discussion has its roots in whether or not there is a genetic basis for PTSD outside the neuropsychological effects of a trauma. More specifically, are there genetic and heritable risk factors which increase vulnerability and/or susceptibility to development of certain psychological disorders, such as PTSD, or are there just general risk factors which increase one’s vulnerability.

Despite the fact that many develop PTSD after experiencing trauma, there are many who endure the exact same circumstances and do not develop the disorder. The difference between these individuals, many claim, is a degree of resilience that is diminished in certain individuals. Anything that diminishes one’s ‘resilience’ is known as a risk factor and can either occur in a stage of pre-traumatic, peritraumatic, or posttraumatic. (Vogt et al., 2010)

Pre-traumatic risk factors include factors such as gender (as females are more likely than males to develop PTSD) and perhaps certain genetic traits and inherited trauma, if these factors are indeed passed down from parent to offspring. Peritraumatic factors include those which deal with the traumatic event itself, as described previously in the dose-response relationship. In a place in which trauma is more prevalent, PTSD is more likely to develop. Lastly, posttraumatic factors include whether or not one had access to therapy and/or social support, etc. Each of these time frames, pre-trauma, during trauma, and post-trauma, effect one’s resilience or lack thereof and thus the onset (or lack of onset) of PTSD. Therefore, if it certain risk factors such as genes can be narrowed down, it is possible that we may find ways to improve resilience among susceptible individuals and prevent development of PTSD.

Psychological

Post-Traumatic Stress Disorder is a response to trauma consisting of various components. Inability to organize memories of trauma and coherently recall the event is normal of trauma memories (Tromp et al., 1995) However, certain characteristics in trauma memory recall are characteristic of this disorder. For example, ‘flashbacks’ which are defined as extremely vivid memories of the trauma in which one experiencing the flashback feels as though they’re reliving the experience, are triggered in subjects with PTSD through external and internal cues. Individuals with PTSD also express extreme dissociation including emotional numbness, depersonalization, derealization etc. (Reynolds & Brewin, 1998). Essentially, PTSD can be defined as a disorder of both fear response and memory.

In terms of memory, memory capacity, content, and process have been studied. Memory capacity refers to amount of information that can be learned, remembered, manipulated, or recalled, and the efficiency with which this can be done. In individuals with PTSD, memory of verbal material is more impaired than viausl material. Additionally, a low score in measurement of verbal memory, without a traumatic event, as well as in general intelligence serves as risk factors for developing PTSD. Memory content refers to what can be remembered from the past. When recalling traumatic events, there are often gaps in recollection of the event. Lastly, memory process is the process by which we recall. For example, many individuals with PTSD practice memory suppression by which they attempt to block out all memory of the trauma from their conscious mind. (Brewin, 2011)

Operant conditioning is a key factor in understanding the role of fearful memory in individuals with PTSD. Operant conditioning is defined as the pairing of a conditioned stimulus/CS (ex: airborne terrorist attack) and an unconditioned stimulus/US (ex: airplane) with a conditioned response/CR, or fear response, (ex: panic attack). A CS is one that under normal circumstances would regularly evoke the CR, but eventually the US becomes conditioned to evoke the CR as well. Therefore, at some point, the CS is no longer needed to evoke the CR, it could be evoked by the US alone. Healthy individuals undergo operant conditioned subconsciously, often associating experiences and emotions with random stimuli present at the time of the event. However, healthy individuals also undergo extinction, a process by which individuals learn that the CS no longer definitely produces the US (ex: there will not be a terrorist attack each time you enter onto an airplane).

However, studies reveal that it this de-pairing of CS and US is not necessarily enough to extinct the original fearful memories. Instead, overcoming fear responses requires the acquisition of new non-fearful memories that can inhibit the original fearful ones. More generally, individuals learn that the US isn’t paired with the original fear response-inducing CS, but is instead paired with a new CS which does not evoke a fear response. (Brewin, 2001)

However, individuals with Post-Traumatic Stress Disorder are not able to perform extinction the original fear response conditioning that occurred at the time of the trauma, or over time with repeated trauma. This is why individuals with PTSD often have spontaneous flashbacks to the traumatic event when they’re exposed to neutral stimuli. For example, someone who has panic attacks each time they go close to an airplane because of an airborne terrorist attack they survived. Thus results in the criterion applied to PTSD such as recurrent, involuntary, intrusive memories and avoidance of trauma-related thoughts, feelings, and external reminders. (American Psychiatric Association, 2013).

Neurobiological

There are various areas of the brain which need to be studied in subject with PTSD, but the disorder deals mainly with fear, learning, and memory. The area of the brain most involved with fear is the amygdala, an area which is responsible for threat-responses including fight-or-flight, the release of stress hormones, and the activation of the sympathetic nervous system. The amygdala is composed of various nuclei (cluster of neurons in the central nervous system) including the central nucleus and the basolateral nucleus.

The central nucleus has been determined to be responsible for fear-conditioned responses through its involvement in the release of cortisol into the hypothalamus, the startle response in the pons, and modulation of the autonomic nervous system (Phelps et al., 2004). Separately, the basolateral nucleus within the amygdala has been found to make the connection between CS and US in operant conditioning (Fanselow & LeDoux, 1999). Lesions in either of these areas lead to either an inhibition in fear-response or fear-conditioning. Where the central nucleus is involved with stimulus-specific fear-responses, the nucleus of the stria terminalis is involved in non-specific anxieties. By means of fMRI and PET scans, presentation of fearful stimuli has been met with amygdala activation. Additionally, recent studies show that there is increased amygdala activation in individuals with PTSD when presented with fear-inducing stimuli, in addition to words related to their trauma. (Jovanovic & Ressler, 2010)

The prefrontal cortex (PFC) is comprised of multiple parts, and those which play into fear-conditioning and association with the amygdala include the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC). In studies in which one needs to ignore certain stimuli and inhibit motor response (ex: one must read the name of a certain color but the word itself is another color), the ACC is found to be ignited. Specifically emotional stimuli that must be ignored are processed in a different area of the ACC than those which are neutral: by the rostral or subgenual area for emotional processing and the dorsal area for neutral tasks. These areas responsible for emotional processing are also ignited during periods of fear.

The mPFC specifically has inhibitory action on the amygdala, playing a role in fear-conditioning extinction outlined previously. Recent fMRI studies show increased activation in the ventromedial PFC during periods of extinction recall post-extinction learning. It has been hypothesized that there is a neural circuit which runs from the basolateral nucleus of the amygdala to the PFC and back to inhibitory neurons in the amygdala. Therefore, during extinction, this circuit is strengthened so that when the extinguished CS is reintroduced, the circuit inhibits the original CR. The ventromedial PFC is also highly ignited when a CS which used to represent danger is changed to representing safety.

Since the prefrontal cortex has been found to modulate the fear responses of the amygdala, the increased and exaggerated fear responses of individuals suffering from PTSD may represent a weakening of this control. In PET scans taken during emotional tasks, individuals with PTSD are seen to have less activation of the ACC, yet have normal functioning of the PFC in non-emotional tasks. However, fMRI studies reveal that individuals with PTSD have increased amygdala activation during extinction learning and decreased ventromedial PFC activation during extinction recall when compared to healthy individuals. However, various studies looking at these regions of the brain produced varied results, something many attribute to differing genotypes with increased or decreased vulnerabilities. (Jovanovic & Ressler, 2010)

Hippocampal volumetric studies have also provided much insight into the pathology of PTSD. The hippocampus is vital for learning, memory, and spatial navigation. The hippocampus also has connections to the amygdala and the hypothalamus and therefore can affect the release of adrenocorticotropic hormones such as cortisol. The hippocampus is also one of the only regions which undergoes extensive neurogenesis into adulthood. (Anand & Dhikav, 2012)

Studies have shown decreased hippocampal volume in various cases of individuals with PTSD, specifically the posterior hippocampus which is responsible for processing, storage, and retrieval of spatiotemporal information. There has also been decreased neurogenesis within the hippocampus, which seems to be combatable with antidepressants (Bremner, 2006). This could be one source of incoherent recollection of the traumatic events. However, other studies failed to find a reduction in hippocampal volume in Holocaust survivors, veterans, or abused women. This variability may result from the different forms of trauma suffered by the subjects, the duration of the trauma, prevalence of comorbid disorders, or genetic differences. Twin studies reveal that PTSD severity is negatively correlated to hippocampal volume in both patients with PTSD and their identical twin who had not been exposed to trauma. Additionally, both trauma-exposed and trauma-non-exposed sibling in pairs with severe PTSD had smaller hippocampal volume than pairs without PTSD (Gilbertson et al., 2002). Therefore, decreased hippocampal began to be seen as perhaps a vulnerability marker or risk factor for development of PTSD rather than an effect of it. (Neumeister et al., 2010) Additionally, the hippocampus has been found to be incredibly plastic in that neurogenesis can be restarted in the presence of anti-depressants, such as SSRIs like Paroxetine or improved social environment. (Bremner, 2006)

The two major neurotransmitters involved in the stress response of PTSD are norepinephrine and cortisol. Therefore, two systems—the corticotropin-releasing factor (CRF) and hypothalamis-pituitary-adrenal (HPA) axis—play an important role. Cortisol (otherwise know as glucocorticoid) is released from the adrenal glands when CRF and adrenocorticotropic hormone (ACTH) are released from the hypothalamus and pituitary, respectively.

The cortisol then acts as negative-feedback to the pituitary, hypothalamus and hippocampus. Cortiosl serves many roles including mediating behavior in fearful situations and triggering other systems (like the noradrenergic system) in response to stress. In response, the noradrenergic system releases transmitters, such as norepinephrine, which increase alert behaviors needed for acute threat. High levels of cortisol seen with stress were associated with an inability to learn new information, which explains why these high levels are thought to decrease hippocampal volume and neurogenesis as the hippocampus is the main site for learning. This decreased hippocampal neurogenesis may be a result of increased cortisol, decreased BDNF, or increased glutamate.

However, these effects are not universal as there have been many studies of patients with PTSD who have lowered levels of cortisol and differing responses to the presence of cortisol and/or norepinephrine. The varied findings revealed that stress sytems change over times and that this change is responsible for the differing levels of cortisol in different studies of PTSD. At a young age, stress is met with increased cortisol levels and norepinehphrine responsiveness. However, when one reaches adulthood, cortisol levels may be normal or low but the responsiveness to cortsiol or norepinhephrine may be high. (Bremner, 2006)

Additionally, extinction relies upon activation of glutamate N-methyl-D-asparatate (NMDA) receptors in the basolateral nucleus. When NMDA antagnoists are introduced into the baseolateral nucleus of the amygdala, fearful memory extinction is inhibited (Baker & Azorlosa, 1996). Similarly, gamma-aminobutyric acid or GABA has been found to play an imporant role in extinction after fear conditioning. Studies have found that blocking GABA insertion into the amygdala impairs the process of extinction. (Lin et al., 2009)