Disclosure: A brief history of PTSD:

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1 Brain Structure and Function in PTSD Joann Mundin, MD, FRCPC, MSc Psychiatrist For presentation at McLeod Law LLP Second Annual Health Care Symposium 2015 Current advances and trends in the diagnosis and treatment of MTBI and PTSD that result from traumatic injuries May 28, 2015 Disclosure: I present the following opinions in the context of my experience as a psychiatrist who provides both treating assessments and care for my patients and non-treating assessments and reports for examinees at the request of third-parties. I have cared for patients since I became a psychiatrist in 2003; I have performed at least 500 non-treating assessments since I started keeping track of my non-treating statistics in As of 2015, I have accepted medicolegal referrals at a rate of approximately 60% defence and 40% plaintiff files. With respect to Post Traumatic Stress Disorder (PTSD), I have assessed both patients and examinees who have developed PTSD from a range of traumas, including sexual assault, catastrophic collisions, catastrophic non-collision accidents, workplace accidents in the oil patch and animal assault. I have assessed examinees who believed they sustained PTSD, but actually did not. I have treated patients with PTSD. I have collaborated with psychologists in the treatment of PTSD. My experience as a psychiatrist has caused me to conclude that PTSD is a serious but usually treatable mental disorder. Due to the controversies associated with the diagnosis and treatment of PTSD, I try to align my clinical opinions as closely as possible to the peer reviewed scientific data published by the academic researchers whose job it is to study PTSD. A brief history of PTSD: An understanding of PTSD has to start by looking back through the history of psychiatry. Unlike many other areas of medicine where scientists have long ago been able to, for example, identify the virus that causes an infection or the genetic mutation that causes a particular syndrome, in psychiatry, we have had to rely mostly on observations and descriptions of abnormal mental states while waiting for the researchers to figure out what is happening in the brain to cause mental illnesses. We have known about the existence of PTSD far longer than we have known about what is happening in the brain to cause PTSD. Historical documents from insane asylums dating back to the 1800s include trauma-related diagnoses 1 that were the forerunners to PTSD such as Exposure in the Army; The War; Shooting of Daughter; Gunshot Wound; Ill Treatment by Husband; and Death of Sons in War as reasons that individuals were admitted for mental health treatment at the time. By the time of the world wars, reports began to emerge from the battlefield of a condition that was termed shell-shock or combat stress disorder. Battlefield doctors recognized a collection of soldiers whom, after encountering the life-threatening horrors of war, developed not only (or not necessarily) 1

2 physical injury, but severe mental injury in the form of mental state changes, often characterized by the thousand yard stare. Long before the development of the sophisticated scientific techniques that are now used to study brain cell structure and function, it was recognized that threat to life or limb affected the mind. However, over the decades, the concept of what we now know as PTSD became diluted and inappropriately expanded. Individuals who encountered unpleasant, routine life circumstances, such as a normal labour and delivery, the end of a dating relationship or a negative performance review at work were being not only diagnosed with PTSD, but also offered expensive and unnecessary treatments for PTSD. The mental health community started to garner negative criticism (appropriately so, I believe) about establishing diagnoses where diagnoses did not exist and recommended needless psychological treatment for routine life events. The concern within the medical mental health community regarding soft mental health diagnoses related to stress was reflected in the updated DSM-5, which is the psychiatric textbook in North America that lists the symptoms required to establish psychiatric diagnoses, including PTSD. When the DSM-5 was released in 2013, it described how PTSD affects the mind, but deliberately did not comment on how PTSD affects the brain. In other words, the DSM - 5 lists PTSD symptoms (such as irritability, insomnia and so on), but does not speak to any of the knowledge that we have about what is happening to the brain cells when they become sick with PTSD. The way that I explain this to my patients is that the DSM-5 will tell you that, if you spill water on your computer, your screen might no longer work or the speakers might buzz; however, the DSM-5 will not explain to you what exactly goes wrong inside the mechanics of the computer to lead to the malfunction. In order to learn more about what is happening to the brain (and not just the mind) in PTSD, we have to look to the lessons coming from the basic science labs. What the scientists tell us about the brain cells and PTSD Basic science refers to the work that is done in laboratories, usually on non-humans, such as bacteria, viruses or lab animals. The results that come from the work of basic scientists will help doctors to understand diseases and treatments. For years, perhaps even decades, the basic scientists have been studying and writing about how both stress (which can be day-to-day, normal kind of worries) and trauma (which is extra-ordinary, severe stress) might affect the brain. Researchers have observed many changes related to the human brain in PTSD, including changes in the brain hormones, changes in the brain chemicals and changes in the brain anatomy 2. However, it is difficult to perform detailed research on human brain cells as long as the human is alive; even after the human is deceased, unless the brain is donated to research, further study of the PTSD-affected brain cells is not possible. Therefore, some of our best understanding of what is happening to stressed out brain cells is coming from the scientists who work with lab mice and lab rats. 2 Sherin et al. Post-traumatic stress disorder: The neurobiological impact of psychological trauma Dialogues in Clinical Neuroscience - Vol 13;No3; 2011

3 During their research, the scientists are able to cause both mental stress and trauma to laboratory mice and rats in different ways, such as by zapping the foot-pad with electricity; preventing the animals from sleeping; exposing the animals to aggressive, bullying animals; removing comfort items from cages for long periods of time; confining the animal to very small spaces for very long periods of time; forcing the animals to swim for long periods of time. The scientists are then able to study what happens to the brain cells of the stressed and traumatized animals compared to the brain cells of animals that never encounter stress. What has been repeatedly shown is the following: 1. Severe and prolonged stress in general will cause brain cells to shrink. Normal brain cells look like trees in a forest, with complicated, fluffy branches. When the brain cells are stressed from extraordinarily stressful events, or from prolonged stressful events, the brain cell branches become thinner, lose their branches all together and retract. When this happens, the brain cells can no longer communicate with each other, and this leads to abnormal brain function. 2. The hippocampus (the memory center in the brain) is believed to shrink in times of severe mental trauma and PTSD. Shrinkage of the hippocampus is a problem. We need our hippocampus to be normal size and normal function so that we can record short term and long term memories. Some researchers believe that an abnormal hippocampus can also lead to signs and symptoms of a depressive mood and anxiety disorder. Individuals with PTSD sometimes experiences symptoms associated with memory, mood and anxiety. 3. Parts of the pre-frontal cortex (called the anterior cingulate cortex, or ACC) are believed to shrink in times of severe mental trauma and PTSD. Shrinkage of the ACC in the pre-frontal cortex is a problem. We need our ACC to be normal in size and function so that we can feel empathy, control our impulses and emotions and have normal blood pressure and heart rate. Individuals with PTSD sometimes experience symptoms associated with anger control and physiological response to mental or environmental events. What the scientists tell us about the treatment of PTSD The choices for treatments in PTSD can appear vast and confusing, in part because there are many more non-evidence based treatments than there are evidence-based treatment for PTSD. A recent review of interventions that purport to prevent PTSD concluded that for most interventions studied, we did not find reliable evidence to support efficacy for the prevention of

4 PTSD or for the reduction of PTSD-related symptom severity 3. For a treatment to be considered evidence-based, there needs to be more than just expert opinion that it works. There are many levels of evidence (some weak and some strong) in medical research beyond expert opinion that a treatment works; some clues that a treatment is considered to have good evidence for its use includes the following: The treatment has been shown in a major scientific journal to be better than no treatment at all. The treatment has been shown in a major scientific journal to be better than a sugar pill (placebo). The treatment has been shown in a major scientific journal to be the same or better than other treatments that are already accepted for use. The findings from the laboratory matches the findings from clinical practice (for example, this is how basic scientists eventually discovered that cells from the pancreas could be given to dogs to treat diabetes; this lead to the use of insulin in humans with diabetes) The basic science labs as well as the clinical researchers are shedding light on which treatments might be more helpful for individuals with PTSD: A. MEDICATIONS for PTSD a. There are currently only two medications that have FDA approval for the treatment of PTSD: 1. Zoloft sertraline, an SSRI antidepressant 2. Paxil paroxetine, an SSRI antidepressant The above two SSRI antidepressant medications make-sense from a basic science perspective. The basic science labs are showing that brain cells that have been shrunken by mental illness (due to PTSD and many other mental illnesses as well) are believed to regrow when treated with the correct medication at the correct dose for the correct amount of time. The basic scientists have been able to demonstrate that certain psychotropic medications turn-on various genes in the brain cells, leading to a domino effect of chemical reactions that allow for new brain cells to regrow. When explaining this 4 to my patients, I compare medication to plant food for a sick plant. When a plant is wilted and the branches appear thin and lifeless, it is sometimes possible to repair the plant branches (the brain cells) back to their healthy state by the addition of the plant-food (medication). 3 Gartlehner G et al. Interventions for the Prevention of Posttraumatic Stress Disorder (PTSD) in Adults After Exposure to Psychological Trauma. Comparative Effectiveness Review No AHRQ Publication No. 13-EHC062-EF. Rockville, MD: Agency for Healthcare Research and Quality; April Anacker et al. Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Molecular Psychiatry (2011) 16,

5 b. There is a small but good evidence-base from the clinical researchers for the use of Prazosin 1 16mg per night in the treatment of the nightmares and insomnia in PTSD 5. c. There is emerging evidence for the use of other psychiatric medications, but none of those medications have the evidence or support that is available for sertraline, paroxetine and Prazocin. B. COUNSELLING (psychotherapy) for PTSD It can be very confusing to look to the academic literature for advice on the best counselling options for a patient with PTSD. It is difficult, but not impossible, to find basic science evidence to guide the choice of counselling options in the treatment of PTSD. Making the choice of counselling even more complicated is the controversy within the psychological community regarding the two counselling options most often mentioned for PTSD: EMDR (Eye Movement Desensitization and Reprocessing) CBT (Cognitive Behavioural Therapy) Over the past several years, researchers have tried to compare EMDR and CBT in an effort to decide which is the best option, with the most recent results (e-publication released in May 12, 2015 ahead of June publication date) concluding that the studies to-date are of limited number and of poor quality 6. From my perspective as a clinician who has to make a recommendation either to my patient or a referring third party, I tend to suggest CBT over EMDR, for two reasons: 1) CBT is more widely available because there tend to be more CBT-providers than EMDR providers and 2) I am more convinced by the current basic science about how CBT might help individuals with PTSD. The idea behind CBT is to help an individual to recognize that a thought (such as a thought about a car crash) can lead to a feeling (such as fear of driving) which will then lead to a problematic behaviour (such as avoidance of getting into a car). Through time-limited CBT (usually no more than 20 sessions), the individual learns to re-evaluate the thoughts and ideas that are causing distress, ensure that the thoughts are appropriate to the current situation and find healthy ways to cope with any emotions that may arise as a result. Of the two most commonly cited counselling options (EMDR or CBT), the researchers have provided two important lines of evidence to support the use of CBT in PTSD: 1. It is possible that CBT (but not EMDR) could regrow shrunken brain cells. This is based on the report from a study of individuals with chronic fatigue syndrome who were found 5 Kung at al. Treatment of nightmares with Prazocin: A systematic review. Mayo Clin Proc Chen at al. Eye Movement Desensitization and Reprocessing Versus Cognitive-Behavioral Therapy for Adult Posttraumatic Stress Disorder. (epub ahead of print) J Nerv Ment Dis 2015;203: 00 00

6 to have smaller sizes to the front parts of their brains at the start of the study. The study participants were given a course of CBT, after which their brain volumes were measured again; an increase in the volume of the front of their brains was found after completion of CBT CBT (but not EMDR) is considered a standard psychological treatment for insomnia 8, which is important, given that anywhere from 70 91% of individuals with PTSD also have insomnia 9. The treatment of insomnia in PTSD (or any health condition) is critical because the long-term consequences of insomnia on the brain cells has been shown by the basic scientists to be similar to what happens to the brains of people with Alzheimer s dementia. What I tell my patients is that during normal sleep, the brain cells start to twist and turn, sort of like a wet towel that is being wrung-out; the twisting and turning allows the brain-cell garbage (called amyloid protein) to leave the brain. However, if the brain does not get restful sleep on most nights, this brain cell garbage starts to collect, and is the same brain cell garbage that clogs the brains of individuals with Alzheimer s dementia. While the brain garbage in Alzheimer s dementia is permanent, the brain garbage (along with the foggy thinking, irritability and other symptoms of sleeplessness) in someone with insomnia is temporary and can be removed once the insomnia is treated. In the case of PTSD, since so many individuals cannot sleep because of worry (often saying they cannot turn-off their mind at night), the value that CBT can offer is to teach the individual how to replace the night-time worry with calming thoughts that promote rather than interfere with sleep. The positive messages that are lost regarding PTSD The epidemiological studies over the years are demonstrating two positive messages that tend to become lost in the discussion on PTSD: 1. According to a 2008 study 10, in Canada, 76 of 100 of us will encounter a trauma bad enough to place us at-risk for PTSD. However, only 9 in 100 of us might go on to develop PTSD in our lifetime. Those people who go on to get PTSD are often exposed to at least 4 or more traumatic events. The most common forms of trauma resulting in PTSD included: Unexpected death of a loved one Sexual assault 7 De Lange et al. Increase in prefrontal cortical volume following cognitive behavioral therapy in patients with chronic fatigue syndrome. Brain(2008), 131, Schutte-Rodin et al Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults. J Clin Sleep Med 2008;4(5): Maher MJ et al. Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management CNS Drugs. 2006;20(7): Post-Traumatic Stress Disorder in Canada. CNS Neuroscience & Therapeutics 14 (2008) c 2008

7 Seeing someone badly injured or killed. 2. The outcomes with PTSD are more likely to be positive than negative and for the majority of individuals, the condition will improve: 1995: In patients who are receiving treatment, the average duration of symptoms is approximately 36 months; in patients who are not receiving treatment, the average duration of symptoms rises to 64 months : We identified three latent classes of symptom change: A large class characterized by a precipitous drop in symptoms from one to five month (Rapid Remitting, 56%), a class characterized by a slow linear decline of symptoms over 15 months (Slow Remitting, 27%) and a class characterized by a failure to remit and no reduction in symptoms (Non-remitting, 17%). 12 The reality that most traumas do not cause PTSD is rarely communicated in the laypress. The fact that PTSD improves in the majority of cases is a message that is not typically communicated in the mainstream media. Treatment failure can become a self-fulfilling prophecy in the clinical setting unless the (currently small) selection of treatments that have an evidence-base are maximized. 11 Kessler et al. Posttraumatic Stress Disorder in the National Comorbidity Survey Arch Gen Psychiatry. 1995;52(12): Galatzer-Levy et al. Early PTSD Symptom Trajectories: Persistence, Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS). PLOS ONE. August 2013 Volume 8 Issue 8