Unraveling PTSD: From Trauma to Dementia

PTSD

The experience of a profound threat can impact us all. For most, it is a transient, although deeply disturbing, experience grounded in

• Reminders of the “exposure,” e.g., nightmares or flashbacks
• Activation – greater irritability, a hyperarousal, that may be expressed as impulsiveness, insomnia, or anger
• Deactivation – a psychologic distancing, numbing, avoidance or even dissociation.

For a significant minority, those alterations last for more than a month, and it is the presence of those signs and symptoms at these later moments that characterize what we call post-traumatic stress disorder, PTSD.

“Why some individuals will develop PTSD following trauma, whereas others do not, is of paramount importance.”

It is difficult to fully construct a “causal chain” between trauma and PTSD, but as you might expect, it appears to be multi-factorial, involving genetic susceptibility, gender, early exposure to trauma, and physical injury. Let me share briefly some of what seems to be the underlying neurobiology.

The hypothalamic-pituitary-adrenal (HPA) axis is central to our stress response. By activating neuronal pathways, hormones, and the adrenal gland, the HPA orchestrates our fight or flee response – overall, more cortisol is released. But in veterans with PTSD and in other “survivors (e.g., Holocaust), there is a “blunted” cortisol response, a hypocortisolism. Whatever the underlying mechanism, in PTSD, there is a dysregulation of the HPA axis's normal response to stress. A related axis involving the hypothalamic-pituitary-thyroid (HPT) helps regulate thyroid hormone. Individuals with PTSD have elevated levels of T3, which may be a source of “subjective anxiety.”

A downstream effect of the dysregulation of HPA is increased levels of norepinephrine (NE), which accounts for the signs of autonomic system arousal – an elevated heart rate and blood pressure, both “cardinal features of patients with PTSD.” The NE lends itself to hyperarousal, a heightened startle reflex, and, along with other perturbations of neurotransmitters, may contribute to impulsivity and intrusive memories. Overall, a host of neurochemicals, including serotonin, GABA, and glutamate, are altered and bring about entangled changes in the presence of PTSD. 

The anatomic areas of the brain, including the hippocampus, amygdala, and cortical regions, demonstrate physical changes over time.

• The hippocampus is linked to impaired memory and an increase in stress response, and “a hallmark feature of PTSD is reduced hippocampal volume.” Whether this alteration is pre-existent or a result of PTSD remains unclear
• The amygdala is involved in emotional processing and “is critical for the acquisition of fear responses.” While no anatomic changes have been seen, functional MRI demonstrates a “hyper-responsiveness” in patients with PTSD and is a genetic trait of those at risk for PTSD.
• There are also reduced volumes in our prefrontal cortical areas associated with the extinction of “conditioned fear.” These are also areas most impacted by traumatic brain injury (TBI), suggesting that damage to these areas contributes to the similarities in presentation between TBI and PTSD.

There are other risk factors felt to be determinants in those developing PTSD.

• Early adverse experiences, even in utero, have been associated with changes in the development of these neurobiological areas and may “program subsequent stress reactivity and vulnerability.”
• Women more frequently suffer from PTSD than men. While the reasons are unclear, there is undoubtedly a plethora of factors, including differences in the type and frequency of trauma, genomic differences, and, of course, sex hormones, which are known to impact the hippocampus and amygdala throughout a woman’s lifetime. In a study of women veterans of Iraq and Afghanistan, women who were pregnant had over twice the incidence of PTSD (21%) as their non-pregnant colleagues.  
• Additional studies of Iraq and Afghanistan veterans demonstrated that bodily injury was also associated with an enhanced risk of PTSD.

A Causal Chain

Considering neurobiological findings in PTSD patients with this overview in mind:

A relative lack of baseline cortisol at the time of psychological trauma may facilitate overactivation of the central CRH-NE cascade, resulting in enhanced and prolonged stress responses. This increased stress responsiveness may be further accentuated by an inadequate regulatory response. An elevation of norepinephrine and lower cortisol may lead to the enhanced encoding of traumatic memories and the lack of inhibition of memory retrieval, both of which presumably trigger re-experiencing phenomena in PTSD. Impairment of the hippocampus “may facilitate generalization of learned fear in contexts unrelated to a previous traumatic exposure and impair the ability to discriminate between safe and unsafe stimuli.” Dysfunction of the amygdala may further accentuate hypervigilance to the point of paranoia and the “further acquisition of fear associations.”

PTSD and TBI

The neurobiological underpinnings of PTSD help explain the emotional, behavioral, and cognitive symptoms and, at the same time, suggest a pathway by which traumatic brain injury (TBI) might also result in PTSD. Studies have demonstrated a strong connection between TBI  and subsequent PTSD. The distinction is important because treatment for these associated but different conditions varies.

Early nonspecific symptoms such as disturbances of sleep, irritability, anger, and general dysphoria can be seen in both conditions. But for those with TBI, the symptoms improve over time, whereas in PTSD, these nonspecific findings may become more and more accentuated. Moreover, as the severity of TBI increases, recovery may slow or stall so that “the failure of symptoms to recede cannot always be taken as an indication of a non-TBI etiology.”

Consider two studies. In the first, slightly more than 1,000 traumatically injured patients were assessed during hospitalization and 3 and 12 months after injury. At one year, 31% had developed a psychiatric disorder, most commonly depression or a generalized anxiety disorder. However, 6% had developed PTSD, and the odds of PTSD were double for those with mild TBI. This is in keeping with the idea that a mild injury leaves many of the neurobiological pathways involved in PTSD dysfunctional but not afunctional.

The second study surveyed 2,525 US Army infantry soldiers 3 to 4 months after returning from deployment in Iraq. 5% report mild TBI, defined as an injury with loss of consciousness, and 10% with an injury and altered mental status. PTSD was diagnosed in 43% of those experiencing loss of consciousness, 27% of those with altered mental states, and 16% in those with non-TBI injuries. 9.1% of the soldiers with no physical injury reported PTSD

PTSD and Dementia

PTSD has been linked with poorer performance on neurocognitive tasks, including attention, memory, processing speed, verbal learning, and executive functions. PTSD appears to be another pathway to dementia or, more appropriately, neurocognitive disorders (NCD), which includes Alzheimer’s Disease and other forms of dementia.

In a study involving 181,000 veterans, 55 or older, with no evidence of baseline dementia over seven years, those veterans with PTSD had “an incident dementia rate of 10.6%, whereas those without had a rate of 6.6%” – a nearly 2-fold higher risk

PTSD’s neurobiology ties it not only to psychological trauma but also to traumatic brain injury and neurocognitive disorders like dementia. The linkage underscores the urgent need for comprehensive understanding and targeted interventions, offering hope for mitigating its long-term impact on individuals' mental health and cognitive well-being.

Source: Post-traumatic stress disorder: the neurobiological impact of psychological trauma Dialogues in Clinical Neuroscience DOI: 10.31887/DCNS.2011.13.2/jsherin

Traumatic Brain Injury and Post-traumatic Stress Disorder: Conceptual, Diagnostic, and Therapeutic Considerations in the Context of Co-Occurrence Journal of Neuropsychiatry and Clinical and Clinical Neurosciences DOI: 10.1176/appi.neuropsych.17090180