Beneath the Surface of the PTSD Iceberg: Evolutionary, Neurobiological and Physiological Perspectives on PTSD

Beneath the Surface of the PTSD Iceberg: Evolutionary, Neurobiological and Physiological Perspectives on PTSD David Diamond Departments of Psychology, Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD University of South Florida Tampa, Florida, USA

PTSD is the Result of Memory x Susceptibility/Resilience Interactions in a Healthy Brain Hyperfunctional Memory Processing

PTSD is the Result of Memory x Susceptibility/Resilience Interactions in a Healthy Brain Resilience Susceptible Hyperfunctional Memory Processing

PTSD is the Result of Memory x Susceptibility/Resilience Interactions in a Healthy Brain Resilience Susceptible Hyperfunctional Memory Processing Recovery Susceptible

PTSD is the Result of Memory x Susceptibility/Resilience Interactions in a Healthy Brain Resilience Susceptible Evolutionary- Biological Perspective on PTSD Hyperfunctional Memory Processing Recovery Susceptible

PTSD is the Result of Memory x Susceptibility/Resilience Interactions in a Healthy Brain Resilience Susceptible Hyperfunctional Memory Processing Evolutionary- Biological Perspective on PTSD Memory-Based Cognitive Treatment Recovery Susceptible

Memory Test: Have you ever seen this creature and what is its name?

This is a tardigrade

Mnemonic: Tardigrades are slow moving

A tardigrade is so slow it s late to class (tardy) causing it to receive a poor grade (tardy-grade) = tardigrade (mnemonic)

Strong Emotional Experiences Produce Flashbulb Memories

How Does a Flashbulb Memory Escalate to a Traumatic Memory? What Conditions Lead to Trauma Escalating to PTSD?

Overt PTSD Symptoms

Overt PTSD Symptoms Evolutionary Perspective on Stress, PTSD and Disease

Our physiological responses to stress enable us to respond to an immediate physical threat to our survival

Mobilization of Resources in Response to a Threat Energy: Increased Epinephrine, Blood Pressure, Heart Rate, Blood Glucose

Mobilization of Resources in Response to a Threat Prepare to be wounded: Immune Stimulation (inflammation), Energy: Increased Epinephrine, Blood Pressure, Heart Rate, Blood Glucose

Pathogenic Bacteria Thrive on Stress (Adrenaline) Enhanced Growth of E. Coli Compared to Lactobacillus in Response to Stress 2.5 2.0 Ratio of E. Coli to Lactobacillus 1.5 1.0 0.5 0.0 No Stress Stress

Mobilization of Resources in Response to a Threat Prepare to be wounded: Immune Stimulation (inflammation), Activate Coagulation Factors Energy: Increased Epinephrine, Blood Pressure, Heart Rate, Blood Glucose

Public Speaking: Stress-Induced Platelet Activation % Increase 200 175 * = 150 125 * 100 75 * 50 25 0 Epi PF4 β-tg Platelet Count Circulation, 71:1129-1134,1985

A Natural Experiment on Traumatic Stress: The Great Hanshin Earthquake Kobe, Japan January 17, 1995 6,434 died; 25,000 wounded; 300,000 homeless

Stress-induced activation of clotting factors Consequences? Clotting factors in people before versus 2 weeks after an earthquake in Japan

Number of new patients with myocardial infarction Consequences of an adaptive process gone awry There was a dramatic increase in the number of heart attacks in this population for weeks after the earthquake occurred

Mobilization of Resources in Response to a Threat Prepare to be wounded: Immune Stimulation (inflammation), Activate Coagulation Factors Powerful Activation of Memory Mechanisms Energy: Increased Epinephrine, Blood Pressure, Heart Rate, Blood Glucose

An Adaptive Cognitive Response to a Threat Gone Awry

With PTSD the Brain is Always Preparing the Body for an Attack Prepare to be wounded: Immune Stimulation (inflammation), Activate Coagulation Factors Powerful Activation of Memory Mechanisms Energy: Increased Epinephrine, Blood Pressure, Heart Rate, Blood Glucose

Adaptive Responses to an Acute Threat

Adaptive Responses: Platelet Activation, Increased Immune Response, Increased Energy (Epi/BP/HR/BG) Adaptive Responses to an Acute Threat

Adaptive Responses to an Acute Threat Adaptive Responses: Platelet Activation, Increased Immune Response, Increased Energy (Epi/BP/HR/BG) Maladaptive Responses: Autoimmune Disorders, Obesity, T2D, Cardiovascular Disease Death

Adaptive Responses to an Acute Threat Adaptive Responses: Platelet Activation, Increased Immune Response, Increased Energy (Epi/BP/HR/BG) Adaptive Responses: Hypervigilance/Activation of Brain Attention and Memory Systems Efficiently Process Information about a Threat Maladaptive Responses: Autoimmune Disorders, Obesity, T2D, Cardiovascular Disease Death

Overt PTSD Symptoms PTSD and Memory - Genetic Susceptibility and Neurobiology Evolutionary Perspective on Stress, PTSD and Disease

Lack of Social Support as a Primary Risk Factor for PTSD/Depression

Interactions: Gene x Trauma Environment x Social Support *

Amygdala Activation is an Essential Component of Emotional Memories

The Amygdala is Essential for the Development and Expression of PTSD

Greater Activation of the Amygdala in People With the Deletion Variant of the α-2b Adrenergic Gene Variant in Response to Evocative Pictures

The Deletion Variant of the α-2b Adrenergic Gene was Associated with Enhanced Memory for Evocative Pictures

The Deletion Variant of the α-2b Adrenergic Gene was Associated with Stronger and More Intrusive Traumatic Memories

Prefrontal Cortex Delayed Post-Natal Development

Less Developed PFC in Adults Maltreated as Children Early Maltreatment/Trauma as a Risk factor for PTSD

Impaired Functioning of the Prefrontal Cortex in PTSD

Imbalance Between PFC and Amygdala Activity in PTSD Reduced PFC Activation in PTSD Increased Amygdala Activation in PTSD

Hippocampus Function: To process and store memories of all of the facts, details and events of our lives.

Chronic Stress Suppresses Neurogenesis and Causes Atrophy of Hippocampal Neurons - Interfering With Memory Issue: Neuronal death and shrinkage of the Hippocampus with Stress/PTSD? Reduced Neurogenesis Stress No Stress Neuronal Atrophy (impaired information flow)

Size of Hippocampus Combat-Exposed Non-Combat-Exposed Twin Twin PTSD Severity

Evidence of Impaired Hippocampal Functioning in PTSD

Trait (global impairment) or State (acute anxiety) effects on Hippocampal Functioning?

Understanding Cognitive Deficits in PTSD by Studying the Debilitating Effects of Test Anxiety (the brain focuses on the threat, rather than the exam)

Overt PTSD Symptoms Neuroendocrine Abnormalities in PTSD PTSD and Memory - Genetic Susceptibility and Neurobiology Evolutionary Perspective on Stress, PTSD and Disease

Change in Neurochemistry in PTSD: Increased Sensitivity to Drugs that Activate Arousal (Norepinephrine) Systems Yohimbine α2 antagonist: increases NE

Magnitude (µv) Hypervigilance in PTSD PTSD Controls Stimulus Intensity (db)

Increased Sympathetic Activation/Arousal and Norepinephrine: Inability to Sleep and Increased Startle Hypervigilance Produces Misery but Enhances Survival

Hans Selye and Cortisol as the Stress Hormone

Insufficient Cortisol in PTSD to Rein in Sympathetic Activation of the Immune System

Overt PTSD Symptoms Neurobiology of Neutral, Emotional and Intrusive Memories Neuroendocrine Abnormalities in PTSD PTSD and Memory - Genetic Susceptibility and Neurobiology Evolutionary Perspective on Stress, PTSD and Disease

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory Name?

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory Tardigrade

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory Neocortex Hippocampus Flashbulb (emotional) Memory Amygdala

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory Neocortex Hippocampus Amygdala Flashbulb (emotional) Memory Contextualization - Amygdala

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory Neocortex Hippocampus Amygdala Flashbulb (emotional) Memory Contextualization - Amygdala Neocortex Hippocampus Amygdala Traumatic (fragmented) Memory

Learning Consolidation/Retrieval Neocortex Hippocampus Neutral (factual/episodic) Memory Neocortex Hippocampus Neocortex Hippocampus Amygdala Amygdala Flashbulb (emotional) Memory Traumatic (fragmented) Memory Contextualization - Amygdala Fragmented and Intrusive Memories Amygdala

Overt PTSD Symptoms Neurobiological Basis of a Non-Pharmacological Treatment Neurobiology of Neutral, Emotional and Intrusive Memories Neuroendocrine Abnormalities in PTSD PTSD and Memory - Genetic Susceptibility and Neurobiology Evolutionary Perspective on Stress, PTSD and Disease

Accelerated Resolution Therapy (ART) Non-Pharmacological Approach to PTSD Therapy A Form of EMDR (Eye Movement Desensitization and Reprocessing)

Reconsolidation: Experiences Occurring During Reactivation of a Memory Can Become Incorporated into the Memory Trauma Memory Retrieved During Therapy Trauma Memory Affect is Blunted Post-Therapy

Intrusive Memory: Repeated Reactivation of a Trauma Memory Trace Hippocampus Intrusive Memories Amygdala

Accelerated Resolution Therapy (ART) Reduced Sympathetic Activation + Imagery Rescripting + Eye Movements PFC - Hippocampus Amygdala

Accelerated Resolution Therapy (ART) Reduced Sympathetic Activation + Imagery Rescripting + Eye Movements PFC - Hippocampus Amygdala Modified Brain Memory Trace Which Generates Less Affect When Retrieved

Overt PTSD Symptoms

Overt PTSD Symptoms Frontal Cortex Amygdala Hippocampus

Thank you - Questions?