Lecture- Understanding Post-Traumatic Stress Disorder (PTSD)

How does it compare to depression? Link

Objectives

By the end of this lecture, students should be able to:

• Understand the basic biology behind stress, fear, and memory formation.
• Define PTSD and describe its epidemiology.
• Discuss the neurobiology and pathology of PTSD.
• Identify the clinical symptoms, diagnosis, and risk factors for PTSD.
• Explore treatment options, including pharmacological and psychotherapeutic interventions.
• Discuss what we know and what remains unknown about PTSD.
• Examine current research trends and future directions for PTSD treatment.

1. Basic Biology of Stress, Fear, and Memory

• The Stress Response:
  • Activation of the hypothalamic-pituitary-adrenal (HPA) axis.
  • Release of cortisol (a stress hormone) from the adrenal glands.
• Fear Conditioning:
  • The amygdala plays a key role in processing fear and emotional memories.
  • The hippocampus integrates contextual information about traumatic events.
• Memory Formation:
  • Normal stress enhances memory; however, severe or prolonged stress can impair memory consolidation and retrieval.
• Neural Connectivity:
  • Dysregulated communication between the prefrontal cortex (reasoning), amygdala (fear), and hippocampus (context) is central to PTSD.

2. Introduction to PTSD

• Definition:
  • PTSD is a mental health disorder that occurs after exposure to actual or threatened trauma, characterized by intrusive memories, hyperarousal, and avoidance behaviors.
• Epidemiology:
  • Affects ~6-8% of the general population.
  • Higher prevalence in populations exposed to violence, combat, or natural disasters.
  • Women are twice as likely as men to develop PTSD.

What We Know

• PTSD results from exposure to traumatic events and involves both biological and psychological components.
• What makes it stand out is how long it invades or impacts a person’s life after the event itself
• Key symptoms: intense sense of distress or physical symptoms when thinking of the incident
• Another hallmark is avoidance
• Certain populations (e.g., veterans, assault survivors) are at higher risk.

What We Don’t Know

• Why some individuals develop PTSD while others exposed to the same trauma do not.
• The exact role of genetics and resilience factors in PTSD vulnerability.

3. Neurobiology and Pathology of PTSD

Post-Traumatic Stress Disorder (PTSD) involves significant changes in brain structure, function, and chemical regulation. These changes explain many of the symptoms experienced by individuals with PTSD, such as heightened fear responses, difficulty distinguishing between safety and danger, and prolonged stress reactions.

Brain Changes

PTSD affects key regions of the brain involved in fear processing, emotional regulation, and memory:

• Hyperactivation of the Amygdala:
  • The amygdala, often referred to as the brain’s “alarm system,” detects threats and triggers fear responses.
  • In PTSD, the amygdala becomes overactive, likely leading to exaggerated fear, heightened emotional reactions, and constant hypervigilance (feeling on edge).
  • This hyperactivity can make individuals feel threatened even in safe environments, contributing to flashbacks and intrusive thoughts.
  • See: Koenigs, M., & Grafman, J. (2009).
• Hypoactivity of the Prefrontal Cortex (PFC):
  • The PFC is responsible for decision-making, regulating emotions, and suppressing fear responses when threats are no longer present.
  • This region is meant to downregulate the amygdala. However, PTSD seems to reduces PFC activity, making it harder to “turn off” fear after a perceived threat has passed.
  • This contributes to symptoms like difficulty calming down, emotional dysregulation, and an inability to focus on non-threatening situations.
• Dysfunction of the Hippocampus:
  • The hippocampus helps process and contextualize memories, distinguishing between past and present experiences and distinguishing between threatening and non-threatening experiences.
  • In PTSD, the hippocampus often shrinks or becomes less functional (“hypoactive”), impairing the ability to differentiate between real and perceived threats.
  • By becoming “hypoactive”, it is unable to downregulate the amygdala
  • This dysfunction explains why traumatic memories feel vivid and intrusive, as the brain struggles to place them in the past.
• Dysregulation of the Anterior Cingulate Cortex (ACC):
  • The ACC plays a key role in emotional regulation, decision-making, and integrating cognitive and emotional responses. It acts as a bridge between the prefrontal cortex and the amygdala.
  • In PTSD, the ACC often shows reduced activity, which can impair its ability to regulate the overactive amygdala and help the prefrontal cortex manage emotional responses.
  • This dysregulation contributes to heightened emotional reactivity, difficulty processing trauma-related cues, and challenges in adapting to stress.
  • The ACC is also involved in error detection and conflict resolution, and its dysfunction can lead to intrusive thoughts and difficulty distinguishing between real and perceived threats.

HPA Axis Dysregulation

The Hypothalamic-Pituitary-Adrenal (HPA) Axis governs the body’s stress response and plays a central role in PTSD.

• Normally, the HPA axis helps the body manage stress by releasing cortisol, a hormone that regulates the fight-or-flight response.

• In PTSD, cortisol regulation becomes abnormal.
  • Low Cortisol Levels: Some individuals show reduced cortisol, which impairs the body’s ability to shut down the stress response.
  • High Cortisol Levels: Others may experience persistently elevated cortisol, leading to chronic stress and physical symptoms like fatigue or immune suppression.
• This dysregulation means the body remains in a heightened state of stress for extended periods, even in non-threatening situations.

Summary: Stress Hormones and PTSD

• The body’s stress response is managed by a system called the HPA axis (Hypothalamic-Pituitary-Adrenal axis), which releases hormones like cortisol to regulate various functions, including heart rate, blood pressure, and immune responses. Normally, cortisol acts like a thermostat, turning the stress response on when needed and off once the situation is resolved. In PTSD, this system becomes dysregulated. Despite low cortisol levels, the brain remains stuck in “stress mode,” leading to heightened inflammation and prolonged feelings of threat or anxiety. This is thought to occur because of increased sensitivity in stress hormone receptors, which overreact even to small amounts of cortisol, disrupting the body’s balance.
• Research shows that individuals with PTSD often have elevated levels of CRH (a hormone that kicks off the stress response) and changes in the sensitivity and number of receptors for cortisol. However, findings about cortisol levels themselves are mixed, with some studies showing low levels, while others find elevated or unchanged levels depending on the timing, trauma type, or patient history. These inconsistencies highlight how PTSD affects not only the stress response but also the entire body, making it difficult to find a one-size-fits-all explanation.
• The current hypothesis suggests that enhanced negative feedback from cortisol-sensitive receptors suppresses the HPA axis too strongly, preventing the body from effectively managing stress. This dysfunction creates a vicious cycle where the brain remains hyperactive, leading to chronic stress and worsening PTSD symptoms. While this hypothesis isn’t fully proven, it provides a framework for ongoing research into understanding and treating PTSD’s biological roots.
• This information is from this paper: Lawrence, S. & Scofield R. H. (2024) Post traumatic stress disorder associated hypothalamic-pituitary-adrenal axis dysregulation and physical illness. Link

Neurotransmitter Changes

Neurotransmitters, the chemical messengers of the brain, are also disrupted in PTSD. These changes affect mood, alertness, and the ability to adapt to stress:

• Norepinephrine:
  • Elevated norepinephrine levels increase alertness and contribute to hypervigilance (constant scanning for danger) and exaggerated startle responses.
  • This chemical is tied to the “fight-or-flight” system, keeping individuals in a heightened state of arousal.
• Serotonin:
  • Serotonin helps regulate mood, emotions, and sleep. PTSD-related changes in serotonin can lead to mood instability, increased anxiety, and difficulty sleeping (e.g., nightmares or insomnia).
• Glutamate:
  • Glutamate is involved in learning, memory, and the brain’s ability to adapt to new information. In PTSD, altered glutamate levels can impair the ability to process and “unlearn” traumatic associations.
  • This contributes to the persistence of fear-based responses to harmless stimuli.
• Dopamine:
  • Dopamine regulates reward and pleasure. PTSD may affect dopamine systems, contributing to emotional numbing, lack of enjoyment in previously pleasurable activities, and difficulty feeling motivated.

Summary of Changes

PTSD is not just a psychological condition; it involves measurable changes in brain structure, hormone levels, and chemical signaling. These biological disruptions help explain why PTSD symptoms are so persistent and why recovery often requires interventions that address both the mind and the body.

What We Know

• PTSD involves disrupted connectivity between fear-related brain regions.
• Stress hormones like cortisol play a significant role in PTSD development.

What We Don’t Know

• Why hippocampal atrophy occurs in some individuals but not others.
• Whether these neurobiological changes are reversible with treatment.

4. Learning Theories and PTSD

• How Learning Shapes PTSD:
  • Learning plays a key role in how PTSD develops and persists. Our brains naturally learn from experiences, but trauma can disrupt this process, leading to maladaptive patterns of thought and behavior.
  • Two major learning theories—classical conditioning and operant conditioning—help explain why PTSD symptoms occur and why they can be so difficult to manage.

Classical Conditioning and PTSD

• Classical conditioning is the process by which we associate a neutral event with a traumatic one. For example:
  • Imagine you hear a loud sound during a traumatic event, like an explosion. Over time, your brain might start associating loud sounds with danger.
  • Even if you’re in a safe environment, hearing a similar sound (like fireworks) can trigger intense fear and make you feel like you’re reliving the trauma.
• This process explains why certain triggers—sounds, smells, or even places—can bring back traumatic memories or cause flashbacks.

Operant Conditioning and PTSD

• Operant conditioning focuses on how behaviors are reinforced by consequences. In PTSD:
  • Avoidance behaviors are a common example. If thinking about or encountering a trauma-related trigger causes distress, avoiding it might feel like a relief in the short term.
  • Over time, this avoidance can reinforce PTSD symptoms by preventing the person from learning that the trigger is no longer dangerous. For example, avoiding crowded places might reduce anxiety temporarily, but it reinforces the belief that crowds are unsafe, making recovery harder.

Implications for Treatment

• Understanding how PTSD is tied to learning can guide treatment. For instance:
  • Exposure therapy helps break the cycle of classical conditioning by gradually exposing individuals to trauma-related triggers in a safe and controlled way, helping the brain learn that the trigger no longer signals danger.
  • Cognitive-behavioral therapy (CBT) addresses the avoidance behaviors reinforced by operant conditioning, encouraging healthier coping mechanisms and reducing avoidance over time.
• By “retraining” the brain, these therapies can help individuals regain control and reduce PTSD symptoms.

Why It Matters

• PTSD is not just about the traumatic event—it’s also about how the brain learns and adapts to it. Recognizing the role of learning in PTSD can help individuals and their loved ones understand that recovery is a process of unlearning old associations and building new, healthier ones.

5. Clinical Symptoms, Diagnosis, and Risk Factors

• Criteria for what is a traumatic event
  1. Exposure to a traumatic event (assault, sudden death, etc.)
  2. Learning about an event that occurred to a family member. For this to qualify for “PTSD criteria”, this event must be traumatic.
  3. Experiencing repeated or extreme exposure to adversive details (ex: first responders dealing with human remains)
• Core Symptoms (DSM-5):
  1. Intrusive Symptoms: Flashbacks, nightmares, intrusive thoughts.
     • memory of the trauma is coming up in unwanted ways
     • flashbacks are less common, but the individual will feel a lost of their sense of time and feel like they are back in that moment in time
  2. Avoidance: Avoiding trauma-related thoughts, feelings, or situations.
     • Avoiding internal experiences (trying not to think about the stressor)
     • Avoiding external things (things that remind you of the traumatic event– people that remind you of it/the location, etc.)
     • Can lead to other concerns such as substance abuse
  3. Negative Alterations in Cognition and Mood: Memory issues, emotional numbness, guilt.
     • Tend to see a general increase in negative emotions and decrease in positive emotions
     • People also tend to start to increase strong negative beliefs about themselves and strong negative beliefs about the world
     • This is one of the more difficult symptoms to treat
     • Sometimes people start to blame themselves or others for the traumatic experience
     • Memory issues: forgetting issues from the trauma because it is painful
  4. Hyperarousal: Hypervigilance, exaggerated startle response, irritability, difficulty concentrating, increase in risky behavior.
     • Hypervigilance: always looking out for danger even if there is no immediate threat

By comparison, other trauma responses may not incorporate the full range of these symptoms or they may be more short-lived (ex: acute stress disorder)

• Diagnosis:
  • Symptoms persist for >1 month and cause significant functional impairment.
• Risk Factors:
  • Severe trauma, lack of social support, pre-existing mental health conditions, genetics.

What We Know

• PTSD symptoms follow predictable patterns, including intrusive memories and hyperarousal.
• Early intervention can reduce long-term impact.

What We Don’t Know

• How to predict who is most vulnerable to chronic PTSD after trauma.

Why do some people get PTSD? Most people experience trauma, but do not develop PTSD. This difference can be influenced by a combination of factors, including the severity of the trauma, individual coping mechanisms, and pre-existing vulnerabilities.

1. Nature of the Trauma: The type and intensity of the traumatic event play a crucial role. Events that involve a direct threat to one’s life or witnessing extreme violence are more likely to lead to PTSD than less intense traumatic experiences.
2. Personal History: Individuals with a history of previous trauma, particularly in childhood, may be more susceptible to developing PTSD after subsequent traumatic events. This is because repeated exposure to trauma can affect the brain’s stress response system, making it harder to cope with new traumas.
3. Biological Factors: Some people may have a genetic predisposition that makes them more vulnerable to stress and anxiety, increasing the risk of PTSD. Differences in brain chemistry, such as levels of cortisol (a stress hormone), can also affect how individuals respond to trauma.
4. Social Support: The availability of social support is a significant protective factor. People who have strong support networks—friends, family, or community—are often better equipped to process and recover from traumatic events. In contrast, isolation or lack of support can increase the likelihood of developing PTSD.
5. Coping Mechanisms: How a person copes with stress and trauma is critical. Healthy coping strategies, such as seeking therapy, talking about the experience, or finding constructive outlets, can help mitigate the impact of trauma. On the other hand, avoidance behaviors, substance use, or denial can exacerbate symptoms and increase the risk of PTSD.
6. Personal Beliefs and Resilience: Individual beliefs and resilience also influence the likelihood of developing PTSD. People who have a positive outlook, a strong sense of purpose, or effective problem-solving skills may be more resilient in the face of trauma, reducing the risk of long-term psychological effects.

6. Gender Differences in PTSD

Research shows significant gender differences in the prevalence, symptoms, and biological responses associated with PTSD. Women are more likely than men to develop PTSD after experiencing trauma, with studies indicating approximately double the prevalence in women compared to men. These differences are influenced by a combination of biological, psychological, and social factors.

Prevalence and Types of Trauma

• Women are more likely to experience interpersonal traumas such as sexual assault or domestic violence, which carry a higher risk for PTSD compared to non-interpersonal traumas like accidents or natural disasters, which are more common in men.
• Men are more likely to face traumas like combat exposure or physical assault, but they are less likely to develop PTSD as a result.

Symptoms and Presentation

• Women with PTSD tend to report more severe emotional symptoms, including:
  • Greater levels of anxiety, depression, and emotional reactivity.
  • Increased likelihood of experiencing dissociative symptoms, such as feeling detached from reality.
• Men with PTSD often exhibit higher rates of externalizing behaviors, including substance abuse and anger outbursts.

Biological and Hormonal Factors

• Hormonal Influences:
  • Differences in estrogen and progesterone levels may make women more susceptible to PTSD. Estrogen has been shown to influence fear extinction, a key process impaired in PTSD.
  • Hormonal fluctuations during the menstrual cycle, pregnancy, or menopause may exacerbate PTSD symptoms in women.
• HPA Axis and Stress Response:
  • Studies suggest that women with PTSD have more pronounced dysregulation of the HPA axis compared to men, including altered cortisol levels and heightened sensitivity to stress hormones like CRH (corticotropin-releasing hormone).

Social and Cultural Influences

• Gender roles and societal expectations may also play a role in PTSD development and coping strategies.
  • Women may feel more pressure socially to internalize their stress, leading to heightened emotional symptoms.
  • Men, on the other hand, are often socially conditioned to suppress emotions, potentially delaying diagnosis and treatment.

Treatment Implications

• Gender differences highlight the importance of tailoring PTSD treatments to individual needs. For example:
  • Women may benefit from therapies that address emotional regulation and trauma-related fears.
  • Men may require additional support for substance abuse or anger management alongside PTSD treatment.

Understanding these gender differences can improve diagnosis, treatment, and support systems for individuals affected by PTSD.

7. Treatment Options

A. Psychotherapy

• The strongest evidence for treating PTSD is psychotherapy (recommended over medications)
• Trauma-Focused Cognitive Behavioral Therapy (CBT):
  • Helps patients process and reframe traumatic memories.
• Prolonged Exposure Therapy:
  • Gradual exposure to trauma reminders to reduce fear.
  • Understanding your symptoms helps you get a sense of control over your reactions.
  • Really targets the avoidance aspect of this.
• Eye Movement Desensitization and Reprocessing (EMDR):
  • Combines exposure therapy with eye movement exercises.

What is Image Rehearsal Therapy (IRT)?

Image Rehearsal Therapy (IRT) is a technique used to help people who have recurring nightmares, especially those caused by trauma or PTSD. It works by teaching you to “rewrite” your nightmares into more positive or less scary versions and then practicing these new versions while you’re awake.

• Nightmares are your brain’s way of processing emotions, but they can get stuck in a loop if they’re tied to trauma. IRT helps break that loop by teaching your brain a new, less distressing way to process those emotions. Over time, this can reduce how often the nightmares happen and how upsetting they feel.

  How Does IRT Work?

  1. Identify the Nightmare: First, you think about a recurring nightmare that bothers you and write it down.
  2. Change the Story: Next, you work on creating a new, less upsetting version of the dream. For example, if your nightmare involves being chased, you might rewrite it so you find safety or even confront what’s chasing you.
  3. Practice the New Dream: After rewriting the dream, you practice imagining it during the day. By rehearsing the new version, your brain can “learn” to use this updated storyline instead of the scary one while you sleep.

• Cognitive Processing Therapy (CPT):
  • Cognitive Processing Therapy is a structured, evidence-based treatment for PTSD that focuses on identifying and challenging unhelpful thoughts related to trauma.
  • In CPT, individuals explore how they process traumatic events and their subsequent beliefs about themselves, others, and the world. This therapy draws on the idea that trauma can disrupt normal patterns of thinking and lead to cognitive distortions.
  • There are three ways to incorporate new information during learning and recovery:
    • Assimilation: Integrating new information into existing beliefs without altering the core belief system. For example, an individual might blame themselves for the trauma (“It happened because I didn’t try hard enough”) to preserve their belief in a just world.
    • Accommodation: Adjusting beliefs to incorporate new, accurate information. In therapy, this might involve shifting from self-blame to understanding that the trauma was not their fault, helping them process the event in a healthier way.
    • Overaccommodation: Overgeneralizing or altering beliefs in a way that becomes maladaptive. For instance, believing “I can’t trust anyone” or “The world is completely unsafe” as a result of the trauma. Overaccommodation can reinforce avoidance behaviors and perpetuate PTSD symptoms.
  • CPT aims to help individuals move from assimilation or overaccommodation toward balanced accommodation, fostering recovery and resilience.
  • See: Resick, P. A., Monson, C. M., & Chard, K. M. (2016).

B. Pharmacological Treatments

• Selective Serotonin Reuptake Inhibitors (SSRIs):
  • First-line medications (e.g., Sertraline, Paroxetine).
• Prazosin: Reduces trauma-related nightmares and hyperarousal.

What We Know

• Psychotherapy, particularly trauma-focused CBT, is highly effective.
• SSRIs help manage symptoms in many individuals.

What We Don’t Know

• Why some individuals do not respond to standard treatments.
• How to target underlying neurobiological dysfunction directly.

8. Current Research and Future Directions

• Neuroimaging: Identifying brain biomarkers for PTSD.
• Pharmacological Innovations: Testing NMDA receptor modulators and MDMA-assisted therapy.
• Resilience Research: Studying genetic and psychological factors that promote recovery.
• Early Intervention: Developing treatments to prevent PTSD immediately after trauma.

9. Summary and Key Takeaways

• PTSD arises after trauma and involves hyperactivation of fear circuits, dysregulated stress responses, and memory impairments.
• Psychotherapy and pharmacotherapy can effectively manage symptoms, but challenges remain in identifying who is most at risk and resistant to treatment.

10. Discussion Questions

1. Why are some individuals resilient to trauma while others develop PTSD?
2. How might brain imaging help diagnose PTSD in the future?
3. What are the pros and cons of pharmacological vs. psychotherapeutic treatments for PTSD?
4. How could early interventions reduce PTSD development in trauma survivors?

References

• Books:
  • Friedman, M. J., et al. (2015). Handbook of PTSD: Science and Practice. Chapter 1 is freely available online
• Articles:
  • Yehuda, R., et al. (2015). PTSD and the HPA axis. Nature Reviews Neuroscience, 16(5), 271–283.
  • Koenigs, M., & Grafman, J. (2009). Post-traumatic stress disorder: The role of medial prefrontal cortex and amygdala. The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 15(5), 540. https://doi.org/10.1177/1073858409333072 (Found on Google Drive)
• Websites:
  • National Center for PTSD: www.ptsd.va.gov