How Post-Traumatic Stress Disorder Affects the Brain



Post-Traumatic Stress Disorder (PTSD) is unique because it is the major psychological disorder for which the cause is considered to be known: a threat to oneself or others that induces a response of fear, helplessness, or horror. PTSD was first formally recognized as a diagnosis in 1980, though it had been around under other postwar names for a long time: soldier’s heart from the Civil War, shell shock from WW I, combat fatigue from WW II, delayed stress from the Vietnam War. Because it was initially largely diagnosed on the basis of patients’ self-reports there was initial suspicion of its legitimacy, but the discovery of biological markers has helped counteract this skepticism and supported widespread acceptance of the disorder. (Pitman et al., 2012) In this article we review the definition and symptoms of PTSD and survey the empirical research into how PTSD affects the brain.


The current view of PTSD syndrome is “a blend of intrusive memories of the traumatic event, avoidance of reminders of it, emotional numbing, and hyperarousal.” (Pitman et al., 2012) PTSD can affect threat perception, threat sensitivity, self-image, and emotional functioning, and disrupt the ability to have healthy relationships or cope with uncertainty, failure, and rejection. Other consequences can be phobias, sleep disturbance, negative mood, anxiety, and attention or concentration difficulties that affect academic and career success. The symptoms need to last at least two weeks and impede functioning or cause significant distress. Statistically, over their lifetimes approximately 10 percent of women and 4 percent of men will develop PTSD. (Greenberg, 2018)


There has been an explosion of biological research seeking to understand PTSD “at organic, cellular, and molecular levels.” Study methods have included “psychophysiological, structural and functional neuroimaging, endocrinological, genetic, and molecular biological studies in humans and in animal models.” Examples of what was studied include “heart rate, skin conductance, facial electromyogram (EMG), and cortical electroencephalographic event-related potentials (ERPs).” In discussions of how people get PTSD as well as how it might be treated, measures were taken of heightened emotional reactivity to trauma-related cues, of exaggerated startle, impaired extinction of memories of trauma, and increased sensitivity to stimulation. Numerous studies looked at resting levels, reactivity, and exaggerated startle responses, comparing people who had PTSD with controls who did not. This included comparisons between PTSD affected and non-PTSD affected twins and war veterans. (Pitman et al., 2012)


Research has tried to understand the neurobiological mechanisms that underly PTSD responses to give PTSD medical grounding and help identify treatments. (Pitman et al., 2012) The research suggests that impaired function in brain areas may be responsible for distortions in threat detection and response, and hamper emotion regulation, leading to PTSD symptoms. (Greenberg, 2018) Hundreds of studies have revealed physical factors in the brain that can be traced to the presence of PTSD. Some may indicate a vulnerability to PTSD, others may indicate its impact. But the sum total of the information, including animal experiments, supports that there is a distinct physical/medical impact affecting PTSD sufferers. (Pitman et al., 2012)


Studies in patients with PTSD show alterations in brain areas implicated in animal studies, including the amygdala, hippocampus, and prefrontal cortex (PFC), as well as in neurochemical stress response systems, including Cortisol and norepinephrine. Results identify a network of brain regions mediating PTSD symptoms, including “medial prefrontal cortex (mPFC), anterior cingulate, hippocampus, amygdala, posterior cingulate, parietal, visual association, and dorsolateral prefrontal cortex.” (Bremner, 2006)


PTSD symptoms are primarily due to dysfunction in the amygdala and the PFC. The amygdala is almond-shaped and situated in the middle of the brain’s temporal lobe. It is meant to detect surrounding threats and activate the “fight or flight” response, and also the sympathetic nervous system to cope with the threat. It helps to store memories related to emotions or threats. The PFC is located in the frontal lobe just behind the forehead. Its purpose is to regulate attention and awareness and make decisions about situational responses. It is also for initiating conscious, voluntary behavior, interpreting the meaning and significance of events, regulating emotions, and inhibiting or correcting dysfunctional reactions. (Greenberg, 2018)


Traumatic events detected as threats trigger the amygdala’s automatic “fight or flight” response which includes the release of  adrenaline, norepinephrine, and glucose to energize the brain and body. If the threat continues the amygdala then contacts the hypothalamus and pituitary gland to release cortisol, while the medial area of the PFC makes a conscious threat assessment and either amplifies or calms the defensive response. Studies of people with PTSD show a hyper reactive amygdala and a less activated medial PFC in response to threats, meaning the reaction of the amygdala is excessively strong while the regulation of the excessive response by the medial PFC is impaired. (Greenberg, 2018)


In people with PTSD, the overactive amygdala releases more norepinephrine that is not well-regulated by the PFC. Hyperarousal and hypervigilance are the result. Because of hyperarousal, those with PTSD can be triggered by events resembling the original trauma, such as viewing an account of a survivor telling a similar story, hearing a loud noise, or seeing someone who resembles their assailant. Because of hypervigilance, people with PTSD may be constantly on edge and on the alert, making their behavior more impulsive. The orbital PFC that can inhibit inappropriate or unnecessary motor behavior has a lower volume and is less activated in people with PTSD, reducing their ability to control anger and impulsive actions when emotionally triggered. This lack of control over reactive anger can have a negative impact on careers and relationships. (Greenberg, 2018)


People with PTSD often say they have excessive negative emotion and difficulty enjoying daily activities and interactions, which could be due to the hyperactive amygdala communicating with the insula, which is associated with introspection and emotional awareness. The amygdala-insula circuit also affects the mPFC and its function of evaluating events and controlling emotions, with overactivity of the amygdala-insula shown to suppress the mPFC, hampering its ability to control negative emotions and to invest events with more positive meaning. (Greenberg, 2018)


Knowing the brain’s normal development path is key to understanding the differences that may be due to pathology, and how they interact. The brain grows in volume for the first five years of life with development of gray and white matter. From age 7-17 white matter increases and gray matter decreases while volume stays the same. The greatest gray matter changes are in the frontal cortex and parietal cortex. The hippocampus, and amygdala appear to increase in size during childhood. During mid-life there is a decrease in gray matter with no change in white matter, and no documentation of changes in the volume of the hippocampus for normal populations except for effects possibly due to menopause and extreme old age. Through the course of these changes trauma at different life stages may affect brain development, and limited studies suggest “differences in the effects of trauma on neurobiology, depending on the stage of development at which the trauma occurs.” (Bremner, 2006)


For example, the fact that the PFC develops later than the amygdala may be why there is increased risk for PTSD associated with younger age in combat veterans. It should be noted that with PTSD defined as “caused by a psychologically traumatic environmental event,” biological abnormalities discovered to accompany PTSD could be assumed to be  “traumatically induced,” but may also have pre-dated the trauma and actually increased the risk of PTSD being triggered. (Pitman et al., 2012)


Studies have shown altered memory function after traumatic stress, as well as changes “in a circuit of brain areas, including hippocampus, amygdala, and medial prefrontal cortex, that mediate alterations in memory.” Memory impairments and reduced ability to perceive safe contexts may be the result of hippocampal dysfunction, while a hyperactive insular cortex through increased “interoceptive awareness” may create a tendency to anxiety. (Pitman et al., 2012) Deficits in verbal declarative memory function were found in patients with combat and child-abuse related PTSD. (Bremner, 2006)


The hippocampus, which is involved in verbal declarative memory, is very stress sensitive.  The most replicated neuroanatomic findings in people with PTSD are diminished volumes of hippocampus and anterior cingulate cortex, which cannot be simply explained by  co-morbid conditions. Smaller hippocampi were found in subjects with PTSD compared to trauma- and non-trauma-exposed subjects without PTSD. The severity of symptoms may affect the scale of differences, since other studies showed that where the smaller hippocampus wasn’t replicated the subjects had a less severe or less chronic case of PTSD. Studies of children with PTSD don’t find a smaller hippocampus, so there may be an impact on the maturing brain of PTSD patients, causing a debate about whether the smaller hippocampus results from trauma exposure or may be a risk factor for “genetic and/or shared environmental” caused PTSD. (Pitman et al., 2012) In other studies those who developed PTSD following an initial trauma had less hippocampal volume compared to PTSD patients who suffered repeated trauma, suggesting a smaller hippocampus may be a vulnerability. (Bremner, 2006) Studies of twins seem to support the smaller hippocampus as being a prior risk factor, but in separate studies, “pharmacological treatment of PTSD with the selective serotonin reuptake inhibitor (SSRI) paroxetine” led to increased hippocampal volume, raising the question of whether it may be an acquired and reversible abnormality. Some studies found that trauma exposure with or without resulting PTSD accompanied a smaller hippocampus. The debate is not resolved between “risk-factor vs. acquired origin of hippocampal diminution in PTSD” and both may play a role. (Pitman et al., 2012)


There is evidence in support of pre-existing vulnerability and neurotoxicity being causes of brain volume reductions in PTSD. (Pitman et al., 2012) Animal studies have shown early stress to contribute to a decrease in branching of neurons in the medial prefrontal cortex. Findings of smaller volume of the anterior cingulate based on MRI measurements in PTSD have been replicated but it is not known whether the effects can be reversed with treatment. (Bremner, 2006)


Among 79 functional PTSD neuroimaging studies, the mid- and dorsal anterior cingulate cortex and bilateral amygdala were the most hyperactivated regions, whereas the vmPFC and inferior frontal gyrus were the most hypoactivated regions. Decreased activity in the vmPFC was associated with increased activity in the amygdala. Neurocircuitry PTSD models hold that in PTSD, the vmPFC fails to inhibit the amygdala, causing attention to be biased toward perceiving threats, as well as causing heightened fear, impairment of the “extinction of traumatic memories,” and deficits in emotion regulation. There appears to be heightened fear expression from the dACC. (Pitman et al., 2012) A graphic illustration of the effects of trauma on regions of the brain can be seen in Figure.

Figure 1.


Lasting effects of trauma on the brain, showing long-term dysregulation of norepinephrine and Cortisol systems, and vulnerable areas of hippocampus, amygdala, and medial prefrontal cortex that are affected by trauma. GC, glucocorticoid; CRF, corticotropin-releasing factor; ACTH, adrenocorticotropin hormone; NE, norepinephrine; HR, heart rate; BP, blood pressure; DA, dopamine; BZ, benzodiazepine.


(Bremner, 2006)



In the development of PTSD there may be a shift in brain state from high-level processing dependent on hippocampus and PFC-mediated working memory, to the “more primitive amygdala-mediated formation of time-locked sensory associations and expression of the species-specific defense response.” A factor in vulnerability may be the impact of individual intelligence and personality on the threshold where this occurs. Numerous neuroregulatory and neuroendocrinological factors may affect such “brain state shifts,” which may vary between individuals and within individuals over time based on life events. These neuroendocrine factors may occur “in both counter-regulatory and synergistic manners” to influence the risk of PTSD as well as the severity of symptoms. They may also offer pathways for new PTSD treatments.(Pitman et al., 2012)


For 25 years, “measures of heart rate, skin conductance, facial electromyogram (EMG), and cortical electroencephalographic event-related potentials (ERPs)” have been applied to the study of PTSD, documenting, among PTSD patients, increased emotional reactivity to trauma-related cues, as well as exaggerated startle, impaired extinction, and increased sensitivity to stimulation. These measures have been used both to predict the risk of a patient suffering from PTSD, and to measure treatment outcomes. “Psychophysiological assessments” of treatment outcome offer more empirical information than a patient’s subjective report, and offer a more objective measuring standard for progress and treatment effectiveness. Possibly the most replicated finding in PTSD is higher heart rate, skin conductance, and facial EMG response during mental imaging of trauma and external cues. Higher heart rates in response to sudden loud noise appear to reflect nervous system sensitization. Symptoms related to re-experiencing trauma “may be conceptualized within a fear-conditioning framework.”  (Pitman et al., 2012)


The full spectrum of “molecular genetic factors” influence or accompany the development of PTSD, but there are not currently definitive findings for a single gene or gene system.(Pitman et al., 2012)


Animal experiments have also been used to provide models for human study where specific traumas could be caused and where the effect on brain tissue studied as it can’t be with humans, offering some promise for identifying pathways for treatments that could help humans. (Pitman et al., 2012)


Because of the extent of replicated scientific information PTSD has become one of the best understood disorders from a biological viewpoint, but a lot of work remains. There is no “gold standard” biomarker. There aren’t enough studies comparing traumatized patients with pre-traumatized people. Existing treatments target symptoms such as depression rather than addressing PTSD directly. It is still true that many treatment successes depend on serendipity. There are some promising signs for treatments but much more research with a systematic approach remains to be done. (Pitman et al., 2012)


Ultimately, research points to two main ways that the brains of people with PTSD differ from those of people who don’t: hyperactive reaction to threat and difficulty controlling or calming anxiety and anger. Treatments address this  by seeking to reduce the amygdala’s reactivity, or increasing the PFC’s capacity to calm it down. Therapists with experience identifying and treating PTSD are the most effective at mitigating patient suffering. (Greenberg, 2018)


Bremner, J. D. (2006). Traumatic stress: Effects on the brain. Dialogues in Clinical Neuroscience, 8(4), 445–461.

Greenberg, M. (2018, September 29). How PTSD and Trauma Affect Your Brain Functioning. Retrieved July 25, 2019, from Psychology Today website:

Pitman, R. K., Rasmusson, A. M., Koenen, K. C., Shin, L. M., Orr, S. P., Gilbertson, M. W., … Liberzon, I. (2012). Biological Studies of Posttraumatic Stress Disorder. Nature Reviews. Neuroscience, 13(11), 769.


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