Chapter 1
Posttraumatic stress disorder: from neurobiology to clinical presentation

Arieh Y. Shalev1 & J. Douglas Bremner2

1Department of Psychiatry, New York University School of Medicine, Langone Medical Center, New York,, NY,, USA

2Departments of Psychiatry & Behavioral Sciences and Radiology, Emory University School of Medicine, and the Atlanta VA Medical Center, Atlanta,, GA,, USA

1.1 PTSD: prevalence, risk factors, and etiology

Posttraumatic stress disorder (PTSD) is a chronic, disabling, and prevalent anxiety disorder. It is triggered by exposure to a psychologically traumatic event, yet only a minority of those exposed actually develop the disorder. Trauma characteristics, as well as genetic, biological, and psychosocial risk factors, contribute to the occurrence of PTSD among survivors of traumatic events. PTSD, therefore is a prime example of gene-environment and psycho-biological interaction. There is a large amount of research in animals on the effects of stress on neurobiology. This has been translated into clinical neuroscience research in PTSD patients. The overarching goal is for our understanding of the neurobiology of the stress response and the long-term effects of stress on stress-responsive systems to inform treatment approaches to PTSD patients. The chapters in this volume, from researchers in all areas of the stress field, including basic scientists as well as research and clinical psychologists and psychiatrists, illustrate the advances in the field that have continued to move from neurobiology to treatment of PTSD. This chapter serves as an introduction to the volume and gives a broad overview of the field.

Posttraumatic stress disorder was first recognized as a distinct psychiatric disorder in the third edition of the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-III; APA, 1981). Subsequent studies have established - and slightly modified - the disorder's symptom structure, evaluated its natural course, and assessed the disorder's biological features. The DSM-IV-TR has been in use for many years, and PTSD symptoms based on that are shown in Box 1.1; however, recently the DSM-5 was released (APA, 2014), and the changes from DSM-IV-TR are described later in this chapter.

Box 1.1 Diagnostic and statistical manual of mental disorders-IV-TR criteria for posttraumatic stress disorder

A. The person has been exposed to a traumatic event in which both of the following were present:

1. 1. The person experienced, witnessed, or was confronted with an event that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others.
2. 2. The person's response involved intense fear, helplessness, or horror. Note: In children this may be expressed, instead, by disorganized or agitated behavior.

B. The traumatic event is persistently re-experienced in one (or more) of the following ways:

1. 1. Recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions. Note: In young children, repetitive play may occur in which themes or aspects of the trauma are expressed.
2. 2. Recurrent distressing dreams of the event. Note: In children, there may be frightening dreams without recognizable content.
3. 3. Acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur on awakening or when intoxicated). Note: In young children, trauma-specific re-enactment may occur.
4. 4. Intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.
5. 5. Physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.

C. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three (or more) of the following:

1. 1. Efforts to avoid thoughts, feelings, or conversations associated with the trauma.
2. 2. Efforts to avoid activities, places, or people that arouse recollections of the trauma.
3. 3. Inability to recall an important aspect of the trauma.
4. 4. Markedly diminished interest or participation in significant activities.
5. 5. Feeling of detachment or estrangement from others.
6. 6. Restricted range of affect (e.g., unable to have loving feelings).
7. 7. Sense of a foreshortened future (e.g., does not expect to have a career, marriage, children, or a normal life span).

D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two (or more) of the following:

1. 1. Difficulty falling or staying asleep.
2. 2. Irritability or outbursts of anger.
3. 3. Difficulty concentrating.
4. 4. Hypervigilance.
5. 5. Exaggerated startle response.

E. Duration of the disturbance (symptoms in criteria B, C, and D) is more than 1 month

F. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning

Specify if:

1. Acute - if duration of symptoms is less than 3 months.
2. Chronic - if duration of symptoms is 3 months or more.
3. With delayed onset - if onset of symptoms is at least 6 months after the stressor.

Posttraumatic stress disorder frequently follows a chronic course and can be associated with recurrences related to exposure to multiple traumas. In addition, PTSD is frequently comorbid with other psychiatric conditions, such as anxiety disorders, depression and substance abuse (Kessler et al., 1995).

Posttraumatic stress disorder is hypothesized to involve the brain's emotional-learning circuitry, and the various brain structures (e.g., prefrontal lobes) and neuroendocrine systems (e.g., the hypothalamic-pituitary-adrenal [HPA] axis) that modulate the acquisition, retention, and eventual extinction of fear conditioning (Bremner & Charney, 2010).

The purpose of this chapter is to bridge the gap between neurobiology and treatment of PTSD that is covered in more detail in the many chapters in this volume related to these topics. This chapter will address issues concerning the acquisition and course of PTSD, including physiological and neuroendocrine factors; recognition and impairment; recent studies of psychotherapy and pharmacotherapy and their effects on neurobiology as well as symptom response; and suggest some directions for research.

1.1.1 The syndrome

Formally, PTSD is defined by the co-occurrence of three clusters of symptoms (re-experiencing, avoidance, and hyperarousal) in an individual who had undergone a traumatic event (Box 1.1).

Symptoms of re-experiencing consist of intrusive, uncontrollable and involuntary instances of re-living the traumatic event, with feelings of fear and panic, and with corresponding physiological responses such as palpitation, sweating or muscular tension. Such "intrusive" experiences often occur upon exposure to cues that remind the person of the traumatic event, but they also occur spontaneously, such as during nightmares or periods of relaxed attention.

Avoidance in PTSD includes phobic avoidance (i.e., of cues and situations that resemble the traumatic event) along with extended avoidance and numbing, expressed as restricted range of affects, diminished interest in previously significant activities, feelings of detachment and estrangement from others and a sense of foreshortened future. The latter clearly resemble symptoms of depression, and may explain the frequent overlap between PTSD and depression.

Symptoms of PTSD hyperarousal include insomnia, anger, difficulties concentrating, hypervigilance and exaggerated startle. Importantly, these symptoms are unrelated to specific reminders of the traumatic event, and constitute an unrelenting and pervasive background of tension and irritability, affecting the patient's entire life.

In the recently released DSM-5, symptoms of PTSD have remained mostly the same, but the trauma definition no longer requires feelings of fear, helplessness, or horror in conjunction with the trauma (APA, 2014). In addition, new qualifying symptoms were added. As can be seen from Box 1.1, symptoms must be present for at least 1 month for a formal diagnosis of PTSD to be made. If symptoms are present for less than 3 months, the disorder is termed "acute," while symptoms enduring beyond 3 months are considered "chronic" PTSD.

The symptom criteria of PTSD have been rather consistent across successive revisions of the DSM. The few changes that were made concerned manifestations of guilt, which figured in DSM-III, and were omitted from subsequent editions, and the presence of bodily responses upon exposure to reminders of the traumatic event, a diagnostic criterion which has been moved from the "hyperarousal" cluster into the "re-experiencing" cluster. More recently, DSM-5 added a new criterion of negative alterations in cognition and mood, which comprises symptoms such as a persistent and distorted blame of self or others, and a persistent...