Anxiety Disorders, Posttraumatic Stress Disorder, and Obsessive-Compulsive Disorder

Franklin R. Schneier

INTRODUCTION

Anxiety is an adaptive emotional state related to anticipation of threat; it can encompass fearful thoughts, symptoms of physiologic arousal, and preparation for fight or flight. Anxiety disorders are characteristic syndromes of maladaptation to various types of anticipated threat. Examples include dangers from predators, interpersonal conflicts, germs, and other hazards. Anxiety disorders are distinguished from mild episodes of anxiety by their persistence and intensity and also by the diagnostic requirement that they cause marked distress or impairment in functioning.

Anxiety disorders have historically included panic disorder, agoraphobia, specific phobias, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder (OCD), acute stress disorder, and posttraumatic stress disorder (PTSD). The recent revision of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), places OCD in a separate category of obsessive-compulsive and related disorders and PTSD in a separate category of trauma- and stressor-related disorders, in recognition of their unique features. Two disorders previously categorized as childhood disorders, separation anxiety disorder and selective mutism, are now also recognized as anxiety disorders that can persist into adulthood.

Anxiety and anxiety disorders may co-occur with neurologic disease through a variety of mechanisms. Neurologic disease processes may cause anxiety symptoms directly by dysregulating function of brain circuits that subserve anxiety. Alternatively, primary neurologic illnesses may lead to anxiety via psychological mechanisms as when visible signs of a movement disorder lead to embarrassment and social anxiety or when an uncertain or poor prognosis leads to anticipatory anxiety. A primary anxiety disorder or its treatment may generate neurologic manifestations, such as syncope secondary to hyperventilation in panic disorder, or a seizure due to abrupt discontinuation of a benzodiazepine. Neurologic and psychiatric conditions may also co-occur secondary to another causal agent as when combat trauma leads to both traumatic brain injury (TBI) and PTSD.

EPIDEMIOLOGY

The historical category of anxiety disorders constitutes the most common type of psychiatric disorder with a lifetime prevalence of over 25%. Anxiety disorders are more common in women by a 2:1 ratio, have an age of onset before 30 years in most cases, and tend to be chronic. Community prevalence rates for individual anxiety disorders range from 5% to 12% for social anxiety disorder and specific phobias to 1% to 2% for panic disorder and OCD with intermediate rates for PTSD and generalized anxiety disorder.

PATHOBIOLOGY

The neural circuits, neurochemistry, and behaviors mediating human anxiety share features with neural systems that mediate withdrawal responses to aversive stimuli across species. In humans, these responses incorporate higher cortical functions such as anxious anticipation and adaptations based on life experiences and culture. Twin studies show heritability of specific anxiety disorders in the range of 10% to 60%, but findings for individual genes explain only very small proportions of the overall risk. Environmental risk factors for anxiety disorders include early childhood trauma and acute stressors, such as interpersonal loss.

Studies in rodents and humans have implicated central nervous system (CNS) fear circuitry, including the amygdala, hippocampus, and prefrontal cortex, in the development and maintenance of conditioned fear; this circuitry is activated when persons with social anxiety disorder, specific phobias, or PTSD are exposed to fear-inducing stimuli (Fig. 150.1). Anxiety disorders also have been shown to be associated with dysfunction of several neurotransmitter systems, including serotonin, norepinephrine, γ-aminobutyric acid (GABA), and glutamate. Dopamine dysfunction has also been reported, and elevated rates of panic disorder, generalized anxiety disorder, and social anxiety disorder have been reported in Parkinson disease. Sympathetic nervous system and hypothalamic-pituitary axis abnormalities have been found across anxiety disorders. Panic disorder has been associated with hyperventilation, hypocapnia, and disordered CO₂ regulation.

The pathobiology of OCD shows some differences from other anxiety disorders. Anatomic and brain imaging evidence suggest hyperactivity in a circuit involving the orbitofrontal cortex, basal ganglia, and thalamus. Acquired lesions in the corticostriato-thalamic circuit, parietal and temporal cortex, cerebellum, and brain stem have been reported to induce compulsivity. OCD has been associated with other neurologic conditions involving the basal ganglia, such as Tourette syndrome, Huntington disease, and Sydenham chorea.

CLINICAL FEATURES

Anxiety disorder patients may present with anxiety, avoidance, physical symptoms, secondary depression, or substance abuse. Complaints of anxiety should be assessed with respect to symptoms and cognitions, frequency and intensity, environmental precipitants, avoidance, and interference with functioning. Some anxiety disorder features can occur across these disorders. Anticipatory anxiety refers to apprehension in anticipation of a feared situation and may include worry, difficulty concentrating, or physical symptoms. Anxiety disorders are often marked by a failure of the habituation that normally occurs during continuing exposure to a feared situation. A panic attack is defined by intense fear that reaches a peak in minutes and includes a group of physical anxiety symptoms, often with feelings of unreality, dizziness, paresthesias, dyspnea, and fear of dying. Phobic avoidance involves excessive avoidance of circumscribed feared situations, and it is often the most directly disabling of anxiety disorder features.

FIGURE 150.1 Brain regions associated with PTSD. PTSD, posttraumatic stress disorder. (From Mahan AL, Ressler KJ. Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder. Trends Neurosci. 2012;35[1]:24-35.)

Anxiety often leads to symptoms of depression, so anxious patients should be evaluated for depressed mood, loss of pleasure, change in weight, sleep disturbance, fatigue, poor concentration, and suicidal ideation. Substance abuse is also common in anxiety disorder patients and may be either a precipitant of anxiety or a response to it. People with anxiety disorders are usually aware that the symptoms are related to an excessive or unrealistic reaction on their part, and in this way, they differ from patients with psychotic disorders with delusional fears.

Anxiety disorders may interact with other medical conditions so that patients with asthma may also experience dyspnea related to panic attacks, and individuals with disorders that attract unwanted attention (e.g., essential tremor) may be impaired by excessive fear of embarrassment as in social anxiety disorder. Medical conditions that can directly mimic anxiety symptoms include hyperthyroidism; hyperparathyroidism; cardiac arrhythmias; reactions to caffeine, cocaine, or marijuana; pheochromocytoma; and vestibular dysfunction.

DIAGNOSIS

See Table 150.1 for key diagnostic features.

PANIC DISORDER AND AGORAPHOBIA

The essential feature of panic disorder, as described in DSM-5, is recurrent unexpected panic attacks followed by persistent concerns or significant changes in behavior related to fear of another attack. Patients with panic disorder are often first seen medically because of fears that they are having a heart attack or stroke. Panic attacks may become cued by specific situations most commonly involving situations in which the person anticipates difficulty escaping or getting help in the event of an attack, such as traveling away from home, being in a crowd, or being alone. When people fear and avoid such situations, the diagnosis of agoraphobia is made.

Case Example of Panic Disorder

A 23-year-old woman presented to the emergency department complaining of 1-hour duration of light-headedness, weak legs, difficulty breathing, tingling sensations in her hands, and fear that she was having a stroke. Symptoms came on suddenly with no specific trigger, although she was feeling stressed after having had an argument with her boyfriend yesterday. Medical and neurologic evaluation was unremarkable. The patient was told that her symptoms were due to anxiety, and they subsequently resolved over a couple of hours. However, the patient developed daily recurrences of attacks over the next week, with fear that the symptoms would be persistent and disabling, even if they were not life-threatening. She called in sick to work and asked a family member to stay with her. Following 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) medication and cognitive behavioral therapy (CBT), her panic attacks remitted, although she continued to experience occasional brief surges of mild anxiety.

TABLE 150.1 Key Diagnostic Features of Anxiety Disorders

Diagnosis	Key Diagnostic Features
Panic disorder	Recurrent unexpected panic attacks
Agoraphobia	Avoidance of situations where escape might be difficult in the event of experiencing panic-like symptoms
Social anxiety disorder	Persistent and excessive fears of negative evaluation in social or performance situations
PTSD and acute stress disorder	After a traumatic event, persistent intrusive thoughts, avoidance of reminders, dysphoria, and hyperarousal
Obsessive-compulsive disorder	Obsessive thoughts and repetitive compulsive behaviors
Generalized anxiety disorder	Excessive anxiety and worry about multiple issues
Specific phobia	Persistent and excessive fear of a specific object or situation
Separation anxiety disorder	Persistent and excessive fear of separation from an attachment figure
Selective mutism	Persistent failure to speak in specific social situations (e.g., school); usually seen in young children
PTSD, posttraumatic stress disorder.

SOCIAL ANXIETY DISORDER (SOCIAL PHOBIA)

Social anxiety disorder, also known as social phobia, is characterized by an excessive fear of social situations due to fears of negative evaluation. The person may avoid social or performance situations or endure them with great distress. Physical symptoms, such as sweating, tremor, and blushing, may be present, but they are not necessary for the diagnosis as per DSM-5. The scope of feared situations may encompass most situations and appear similar to extreme shyness or may be limited to performance situations, such as public speaking. Social anxiety disorder is distinguished from normal shyness by its greater persistence and severity and its associated distress or impairment. Persons with social anxiety disorder often have difficulty participating in classroom settings or work meetings, dating, or engaging in social gatherings.

POSTTRAUMATIC STRESS DISORDER AND ACUTE STRESS DISORDER

Stress disorders occur in persons exposed to a traumatic event in which the person experienced, witnessed, or was confronted with actual or threatened death, serious injury, or sexual violence to self or others. PTSD features according to DSM-5 include more than 1 month of (1) intrusive memories, dreams, or flashbacks or intense psychological and physiologic distress at exposure to reminders of the trauma; (2) avoidance of stimuli associated with the trauma; (3) alterations in cognition or mood, such as self-blame or inability to experience positive emotions; and (4) symptoms of increased arousal, such as hypervigilance, insomnia, poor concentration, irritability, or reckless behavior. Acute stress disorder is diagnosed when a similar syndrome is present in the month after trauma exposure, and it may progress to PTSD. When a TBI cooccurs, PTSD symptoms may overlap TBI-related neurocognitive symptoms.

OBSESSIVE-COMPULSIVE DISORDER

OCD is defined in DSM-5 by recurrent obsessions or compulsions that are time-consuming (more than 1 h/day) or cause significant distress and impairment. Obsessions are recurrent and persistent thoughts, urges, or images that are experienced as intrusive and unwanted and cause marked anxiety or distress. The individual attempts to ignore or suppress the obsessions or to neutralize them with some other thought or action. Insight into the truth of obsessive beliefs may vary. Compulsions are repetitive behaviors, such as washing or checking, or mental acts, such as counting, that an individual feels driven to perform in response to an obsession or according to rigid rules. The individual may have ideas that the behaviors prevent distress or that they somehow prevent a dreaded event (e.g., death of a loved one). However, these behaviors are not realistically connected with what they are intended to prevent, or they are clearly excessive. Up to 30% of individuals with OCD have a lifetime tic disorder, and in such cases, the diagnosis should be specified as tic-related.

GENERALIZED ANXIETY DISORDER

Generalized anxiety disorder is characterized, according to DSM-5, by excessive anxiety and worry about a number of events or activities occurring more days than not for at least 6 months. The individual finds it difficult to control the worry, which is associated with three or more of (1) restlessness or feeling keyed up, (2) fatigue, (3) difficulty concentrating, (4) irritability, (5) muscle tension, and (6) sleep disturbance. Generalized anxiety disorder is highly comorbid with depression.

SPECIFIC PHOBIAS

Persons with a specific phobia exhibit persistent fear of a specific object or situation, exposure to which evokes a fear response out of proportion to the actual danger. As specified in DSM-5, common types are the following: animal (e.g., spiders or dogs), natural environment (e.g., storms, heights), situational (e.g., airplanes, enclosed places), and blood-injection-injury (e.g., needles, dentist). A vasovagal response has been specifically associated with blood-injection-injury phobia.

SEPARATION ANXIETY DISORDER

Separation anxiety disorder is characterized in DSM-5 by an excessive fear of separation from an attachment figure as evidenced by at least three of the following: excessive distress related to separation, excessive worry about harm to an attachment figure, excessive worry about an untoward event that results in separation, reluctance to go out (e.g., to work), reluctance to be alone, reluctance to sleep away from an attachment figure, nightmares about separation, and physical symptoms when separated. Adults often worry about a significant other or a child.

SELECTIVE MUTISM

Selective mutism is generally diagnosed in young children but may persist into adulthood. As described in DSM-5, the diagnosis is based on observation that an individual manifests a persistent failure to speak in specific social situations (e.g., school) despite speaking in other situations. The behavior interferes with functioning and is not due to a lack of knowledge of the spoken language
or a communication disorder (e.g., childhood-onset fluency disorder). A child with selective mutism may be unable to offer an explanation for his or her silence, although high levels of social anxiety often appear to be associated with this reticent behavior.

ANXIETY AND NEUROLOGIC DISEASE: COMORBIDITY AND DIFFERENTIAL DIAGNOSIS

Anxiety disorder symptoms can overlap greatly with symptoms of a variety of neurologic disorders, including movement disorders, epilepsy, or cerebrovascular disease. For example, tremor is a common manifestation of anxiety, and it is particularly common in performance situations for individuals with social anxiety disorder. Light-headedness, occasionally even leading to syncope, is common during panic attacks. Panic-related light-headedness is usually of short duration and accompanied by dyspnea, hyperventilation, and intense fear. Paresthesias, tinnitus, vertigo, impaired concentration, derealization, and depersonalization may also occur during panic attacks or other periods of high anxiety. Importantly, the presence of psychopathology does not rule out the presence of concurrent neurologic disorder, and symptoms of a primary neurologic disorder, such as tremor or vertigo, may be exacerbated by situational anxiety. When a comorbid anxiety disorder complicates a neurologic disorder, treatments targeted at each condition may be necessary.

Obsessive-compulsive symptoms have been specifically associated with several neurologic disorders sharing dysfunction of frontostriatal circuitry, including Huntington disease and Gilles de la Tourette syndrome. In patients with Huntington disease, obsessive-compulsive symptoms, particularly obsessive checking, pathologic impulses, and compulsive rituals, have been reported in 15% to 50% of cases. OCD symptoms are also elevated in persons with the genetic mutation for Huntington but who have not yet met criteria for the diagnosis.

Tics have a compulsive quality, and like compulsions, if resisted, they result in internal tension that is relieved by performance of the behavior. The compulsions of OCD, however, are often accompanied by a complex thought process (e.g., need to relieve a sense of contamination) that seems to motivate the compulsive behavior. Compulsions that are present in patients with Tourette syndrome tend to be related to symmetry, counting, or “just right” thoughts and less likely to relate to fears of contamination or harm to others. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a controversial variant of Gilles de la Tourette syndrome and childhood-onset OCD in which both conditions may be associated with the development of an immune response against group A β-hemolytic Streptococcus.

In epilepsy, there is an increased rate of anxiety disorders, and panic disorder symptoms are the anxiety symptoms most likely to be generated directly by a seizure. Patients with primary panic attacks are less likely than seizure patients to experience automatisms, impaired consciousness, or déjà vu experiences and more likely to have accompanying phobias, depression, and anticipatory anxiety.

Dementia is accompanied by elevated rates of anxiety, often in the form of generalized anxiety disorder symptoms. Rates of anxiety symptoms may be particularly greater in vascular dementia and frontotemporal dementia. The presence of anxiety in dementia is associated with a variety of worse outcomes, including more impairment in quality of life, activities of daily living, nighttime awakenings, and neuropsychological performance.

Males with the genetic syndrome fragile X commonly experience symptoms of multiple anxiety disorders, particularly social anxiety symptoms of poor eye contact and excessive shyness. They also have elevated rates of separation anxiety, panic attacks, and agoraphobia. Compulsive behaviors are present in most patients, but these often involve pleasurable activities rather than the unwanted compulsions characteristic of OCD.

In patients with multiple sclerosis, anxiety disorders occur at three times the rate of the general population. Generalized anxiety disorder, OCD, panic disorder, and social anxiety disorder have been found to be elevated in some studies. Anxiety is associated with confirmed exacerbations and pseudoexacerbations of multiple sclerosis and with greater impairment, although it has not been specifically linked to progression of brain lesions.

TREATMENT

GENERAL APPROACHES TO ANXIETY DISORDERS

Psychological and pharmacologic treatments (Table 150.2) have well-established efficacy for anxiety disorders. The two best established first-line treatments for most of the anxiety disorders are CBT and SSRI medications, based on dozens of controlled trials in specific anxiety disorders. Other psychotherapies, such as short-term psychodynamic therapies, and other medications, such as benzodiazepines, have been demonstrated efficacious in certain anxiety disorders. This section will describe the general features of CBT and classes of medication used for anxiety disorders, as well as their unique adaptations for specific anxiety disorders.

CBTs for anxiety disorders are short-term psychotherapies based on the observation that patients manifest cognitive distortions (irrational negative thoughts) that maintain anxiety and avoidance behaviors, and that deny them opportunities to disprove those fears or to experience habituation of anxiety symptoms. Components of this therapy may include cognitive restructuring, exposure, and relaxation techniques. Typically, an active therapist helps the patient identify his or her cognitive distortions and avoidance behaviors and introduces alternative approaches for coping with feared situations. Therapist and patient collaborate to conduct exposures to the feared situations in the presence of the therapist and through homework assignments. As the patient uses new coping skills to manage the anxiety induced by the exposure without resorting to avoidance or rituals, new learning takes place and the habitual cycle of fear and avoidance recedes. A far smaller body of evidence exists for efficacy of other psychotherapy approaches to anxiety, including psychodynamic therapy. Disorder-specific features of CBT and other psychotherapies are discussed below under specific disorder sections.

SSRIs and serotonin-norepinephrine inhibitors (SNRIs) have emerged as first-line treatments for each of the anxiety disorders (with the exception of specific phobias) based on efficacy and acceptability. No single SSRI has been shown to be superior to others, although individuals often have different responses to different agents. Dosages are similar to those recommended for treatment of depression. Responses typically become apparent after 2 to 4 weeks of treatment, but an adequate acute trial may require 8 to 12 weeks of treatment, and nonresponders should have the dosage gradually increased to the maximum as tolerated. Common side effects include nausea, insomnia, fatigue, weight gain, and sexual dysfunction. Treatment guidelines tend to recommend that responders to an acute trial of medication be maintained on the effective dose for
6 to 12 months, and when medication is discontinued, it should be tapered to minimize risk of withdrawal symptoms and relapse.

TABLE 150.2 Medications Used in the Treatment of Anxiety Disorders

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