Anxiety Disorders and Related Disorders
A woman is approached by a strange man on a dark street. Her body responds rapidly. Her heart rate increases, she starts shaking and sweating, and she has an intense desire to run to safety. Another woman experiences the same sympathetic nervous system responses whenever she leaves her home, despite the fact that there is no one approaching her.
Although the terms fear and anxiety are often used interchangeably, their meanings are actually quite different. The first woman is responding with fear, a normal reaction to a real external threat. The second woman is responding with anxiety; she feels threatened, but the source of the threat is not known, not recognized, or inadequate to account for her symptoms. The first woman quickly calms down when she finds refuge and the source of her fear is removed. Because the source of the second woman’s anxiety is obscure, her symptoms are likely to persist and may even intensify over time.
• OVERVIEW OF ANXIETY DISORDERS
All anxiety disorders are characterized by physiological and psychological symptoms of fear without adequate cause. Because most people experience transient anxiety at some time in their lives, normal anxiety must often be distinguished from an anxiety disorder. To diagnose an anxiety disorder, the symptoms must be present for an extended period (often at least 6 months), interfere with a person’s normal functioning, and cause significant distress.
General characteristics
The physiologic manifestations of anxiety include sympathetic nervous system symptoms such as shakiness, sweating, mydriasis (pupil dilation), and the subjective experience of tachycardia or irregular heartbeat, which patients may refer to as “palpitations.” Anxious patients also commonly report gastrointestinal symptoms (e.g., diarrhea) and urinary disturbances (e.g., increased frequency). The hyperventilation that can accompany these sympathetic responses can lead to dizziness and syncope (fainting), as well as tingling sensations in the extremities and loss of sensation or numbness around the mouth. Symptoms of anxiety can be situational or free-floating. Situational anxiety is caused by an overreaction to an identifiable, external, environmental stressor, whereas free-floating anxiety has no particular external trigger. In both types of anxiety the patient typically recognizes that his symptoms are more severe than the situation warrants (i.e., he has insight).
DSM-5 classification of anxiety disorders
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) classification of anxiety disorders includes
Generalized anxiety disorder (GAD)
Panic disorder
Specific phobia
Social anxiety disorder (social phobia)
Agoraphobia
Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) while no longer classified under anxiety disorders in DSM-5, are discussed in this Chapter as related disorders. The diagnoses anxiety disorder due to another medical condition and substance/medication-induced anxiety disorder are given if a medical illness or substance use or withdrawal is the main cause of the anxiety symptoms.
The anxiety disorders and related disorders are distinguished from each other by the presence or absence of an obvious environmental stressor (present in the phobias, PTSD, and ASD; absent in panic disorder, OCD, and GAD), as well as the pattern of symptom appearance and disappearance
(e.g., acute in panic disorder; chronic in GAD). Descriptions of the anxiety disorders and related disorders follow in subsequent sections; specific examples of patients with each disorder are given in Table 15-1.
(e.g., acute in panic disorder; chronic in GAD). Descriptions of the anxiety disorders and related disorders follow in subsequent sections; specific examples of patients with each disorder are given in Table 15-1.
Etiology
The anxiety disorders are among the most commonly treated mental health problems. Both psychosocial and biological factors are involved in their etiology. Psychosocial factors include maladaptive learning, which results in fear of a harmless thing or situation (see Chapter 9) and prior exposure to an extreme stressor. As evidence for this association, D-cycloserine, an antibiotic that apparently increases memory and the speed of learning, is helpful for some patients with specific phobias (Davis et al., 2005). Biological factors include genetics and gender. Anxiety disorders are more common in the family members of patients than in the general population, and their concordance rates are higher in monozygotic than in dizygotic twins. Compared with men, women are two to three times more likely to have panic disorder, twice as likely to develop PTSD when exposed to an extreme stressor, and slightly more likely to have GAD.
table 15.1 PATIENT EXAMPLES OF ANXIETY DISORDERS AND RELATED DISORDERS | ||||||||||||||||
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Neurobiological associations
Altered neurotransmitter activity is associated with symptoms of anxiety; specifically, decreased activity of serotonin (5-HT) and γ-aminobutyric acid (GABA); decreased GABA-benzodiazepine receptor binding (Malizia et al., 1998); and increased activity of norepinephrine and glutamate (see Chapter 5). Recently, it was shown (Gleason et al., 2010) that deletion of the 5-HT1A receptor gene and low 5-HT1A receptor binding are risk factors for anxiety and depression and are associated with the relatively high heritability of the anxiety disorders. Also, the learning and extinction of fear responses are blocked by antagonists at the glutamatergic N-methyl-D-aspartate (NMDA) receptor and increased, as noted previously,
by D-cycloserine, a partial agonist at the NMDA receptor (Hoffmann et al., 2006).
by D-cycloserine, a partial agonist at the NMDA receptor (Hoffmann et al., 2006).
Neuroanatomically, the locus ceruleus, the site of noradrenergic neurons; the raphe nuclei, the site of serotonergic neurons; the temporal cortex; the frontal cortex; the anterior and posterior cingulates; and the caudate nucleus (particularly in OCD) are implicated in the development of anxiety disorders (see Chapter 5, Figs. 5-4 and 5-5).
Differential diagnosis
Organic causes of the symptoms of anxiety include excessive caffeine intake, substance use and withdrawal, hyperthyroidism, vitamin B12 deficiency, hypo- or hyperglycemia, anemia, and pheochromocytoma, an epinephrine-secreting adrenal medullary tumor. Because symptoms of anxiety (e.g., shortness of breath, chest discomfort, tachycardia, and sweating) also occur in cardiovascular disorders such as arrhythmias and respiratory disorders such as chronic obstructive pulmonary disease, these disorders must also be ruled out.
Anxiety is marked in many depressed patients, and patients with anxiety disorders often show comorbid major depressive disorder or dysthymic disorder (see Chapter 13). It can therefore be difficult to distinguish between anxiety and depressive disorders. The close biological association between these groups of disorders is supported by research showing that neuroendocrine abnormalities and electroencephalographic changes during sleep (see Chapter 7) are similar in patients with OCD and major depressive disorder and that both disorders respond to selective serotonin reuptake inhibitors (SSRIs) and other antidepressants.
case 15.1
THE PATIENT
A 45-year-old woman says that she frequently feels “nervous” and often has an “upset stomach,” which includes heartburn, indigestion, and diarrhea. Physical examination (including blood pressure) and laboratory values (including thyroid function tests) are unremarkable. She notes that she often finds herself worrying about whether she will lose her job and whether her elderly parents will become ill. She says that she has been “a worrier” since she was a teenager and notes that other family members also tend to worry a great deal.
COMMENT
This patient is showing the symptoms of GAD. She has a chronic, subjective sense of fear with no obvious precipitant, unexplained gastrointestinal problems, and a family history of anxiety. She does not have panic disorder because, although her anxiety symptoms have lasted at least 6 months, there have been no distinct attacks. Normal thyroid function and blood pressure, as well as the family history of anxiety indicate that physiological causes of her anxiety symptoms, such as hyperthyroidism and pheochromocytoma, are unlikely.
MANAGEMENT
Antianxiety agents such as buspirone (BuSpar) and antidepressant agents such as paroxetine (Paxil), venlafaxine (Effexor), duloxetine (Cymbalta), and doxepin (Adapin, Sinequan) are effective for the longterm treatment of patients with GAD. Unlike benzodiazepines, these agents do not cause dependence or tolerance. If benzodiazepines are used to treat this patient, the most effective ones are those that have an intermediate length of action such as lorazepam (Ativan), because they have less addiction potential than short-acting agents yet work quickly enough to relieve the patient’s acute symptoms.
Anxiety disorders must also be distinguished from the prodrome and psychotic phases of schizophrenia where anxiety is often prominent (see Chapter 12) and hypochondriasis, in which there is unfounded but significant distress about having a serious illness (see Chapter 16).
• GENERALIZED ANXIETY DISORDER (GAD)
Characteristics
Patients with GAD have persistent symptoms of anxiety, including hyperarousal and excessive worrying over at least a 6-month period. Their symptoms cause them significant distress but cannot be related to a specific person or situation (i.e., are “free-floating”).
Occurrence and prognosis
GAD is present in about 3% to 5% of the population and is commonly comorbid with major depression. In about 50% of patients, the onset of GAD occurs in childhood or adolescence. Symptoms are chronic and tend to worsen during stressful times. Treatment is often needed indefinitely, although some GAD patients become relatively asymptomatic over time.
• PANIC DISORDER
Characteristics
Panic disorder is characterized by episodic panic attacks, periods of intense anxiety that have a sudden onset and increase in intensity over an approximately 10-minute period. A panic attack commonly lasts about 30 minutes. During an attack, the patient has striking cardiac and respiratory symptoms that lead him or her to believe that he or she is about to die. Although mitral valve prolapse is often found in patients with panic disorder, no causal relationship between the two conditions has been demonstrated. Between attacks, the patient often develops anticipatory anxiety, an intense fear of having another attack, which further limits his or her functioning.
When panic disorder becomes associated with agoraphobia, panic attacks are associated with fear and avoidance of public places or situations where escape is impossible or help is unavailable. For example, a patient with panic disorder and agoraphobia may have a panic attack whenever he goes outside alone but not when he goes out with his wife. Patients may avoid shopping malls, theaters (unless they sit at the end of the row near the door), and driving in heavy traffic.
For experimental diagnostic purposes, a panic attack can be induced in a panic disorder patient by intravenous administration of sodium lactate or by hyperventilation or inhalation of CO2 (see Chapter 6).
Occurrence and prognosis
Panic disorder has a lifetime prevalence of 1.5% to 3.5%, and the mean age of onset is 25 years. Genetic factors and social factors, such as divorce or marital separation in the patient’s recent past, are involved in the etiology of panic disorder. When compared with the general population, adults who have panic disorder with agoraphobia are more likely to have experienced separation anxiety disorder in childhood (see Chapter 2). The course of panic disorder is chronic, with recurrent episodes and an increased risk of depression and suicide.
table 15.2 SUBTYPES OF SPECIFIC PHOBIA | ||||||||
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