A. Biomedical Influences


Significant genetic component, especially for panic disorder, generalized anxiety, and phobias.

Temperament, which has genetic roots, is a broad vulnerability factor for anxiety disorders.


The inhibitory transmitter γ-aminobutyric acid (GABA) occupies ~40% of all synapses and is implicated in the anxiety disorders

Exposure to a stressor activates the release of an endogenous opioid, β-endorphin, which is coreleased with adrenocorticotropic hormone.

B. Psychological and Social Influences

Family dysfunction and parental psychopathology are involved in the development and maintenance of anxiety. Families of anxious children are more involved, controlling, and rejecting, and less intimate than are families who do not manifest anxiety. Parents of anxious children promote cautious and avoidant child behavior.

Behavioral and cognitive explanations define anxiety as a learned response. Anxiety develops in response to neutral or positive stimuli that become associated with a noxious or aversive event. Fearful associations develop from the situational context and the physical sensations present at the time. The patient may generalize (ie, classify objects and events in terms of a common characteristic) and thereby establish new cues to trigger anxiety. Previously neutral situations become feared and avoided. By avoiding anxiety-arousing stimuli, anxiety is diminished.

As panic and avoidance become more chronic, the behaviors involved become more habitual and awareness of one’s thoughts in relation to these anxiety states diminishes. Information-processing prejudices such as selectively attending to threatening stimuli become involuntary and unconscious. A person’s appraisal of an event, rather than intrinsic characteristics of that event, defines stress, evokes anxiety, and influences the ability to cope. Failure to cope elicits fear and vulnerability.



Kagan  J, Snidman  N Early childhood predictors of adult anxiety disorders. Biol Psychiatr. 1999; 46:1536. 
[PubMed: 10599481] 




anxiety due to drugs should be excluded.

Questioning should then focus on whether anxiety comes on as a sudden attack without warning as is characteristic of panic disorder or is more predictably associated with known triggering objects, events, or circumstances. When anxiety triggers are diverse and persistent, GAD is the likely diagnosis. When they are specific and known, phobias, OCD, or PTSD is likely. There are also standard screening tools available for GAD and panic disorder like the Generalized Anxiety Disorder-7 questionnaire, Shedler Quick PsychoDiagnostics Panel (QPD Panel), and the Anxiety Screening Questionnaire (ASQ-15). See Figure 63–1 for the diagnostic approach algorithm for anxiety.


An important starting point is to keep anxiety disorders in mind, particularly in patients who have a history of unexplained medical symptoms, high utilization of healthcare resources, major life stresses, prior physical or psychological trauma, depression or substance abuse, or disruptions in social or occupational functioning.


Content 9



B. Diagnostic Criteria

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) differentiates several anxiety disorders. Diagnostic criteria for each disorder are presented below.

1. Separation anxiety disorder

This disorder Involves excessive anxiety or fear concerning separation from those whom the individual is attached to.

2. Selective mutism

This disorder involves a consistent failure to speak in specific social situations where there is an expectation to speak despite speaking in other situations.

3. Specific phobias

These phobias involve marked fear or anxiety about a specific object or situation (eg, flying, heights, receiving an injection).

4. Social anxiety disorder

This condition is characterized by marked fear or anxiety about one or more social situations where the individual is exposed to possible scrutiny by others. The individual fears that s/he will act in a certain way or show anxiety that will be negatively evaluated and avoids these social situations or endures them with intense fear or anxiety, out of proportion to the actual threat.

5. Panic disorder

The attack involves an abrupt surge of intense fear or discomfort that reaches a peak within minutes and can be recurrent and unexpected. Symptoms include nausea, dizziness, lightheadedness, tingling sensations, feelings of unreality or being detached from oneself, fear of going crazy, and fear of dying.

6. Agoraphobia

This is a marked fear or anxiety about using public transportation, being in open or enclosed spaces, being in a crowd, or being outside alone.

7. Generalized anxiety disorder (GAD)

At least 6 months of persistent and excessive anxiety and worry occur on most days, with difficulty controlling the worry. Symptoms include restlessness, being on edge, being easily fatigued, difficulty concentrating, irritability, muscle tension, and sleep disturbance. Several validated tools have been developed to screen for GAD, including the two-item and seven-item Generalized Anxiety Disorder scales (GAD2, GAD7). These self-report questionnaires are easy to use and can assist primary care physicians in assessing the severity of GAD as well.

8. Substance/medication-induced anxiety disorder

Anxiety is a direct physiologic consequence of a drug of abuse, medication, or exposure to a toxin.

9. Anxiety disorder due to another medical condition

Panic attacks or anxiety predominate, and there is evidence that the disturbance is the direct pathophysiological consequence of another medical condition.

10. Adjustment disorder with anxious mood

Clinically significant symptoms of anxiety occur in response to an identifiable stressor within 3 months after onset of the stressor and resolve within 6 months after termination of the stressor. However, symptoms may persist longer if they occur in response to a chronic stressor (eg, a disabling chronic medical condition) or to a stressor that has enduring consequences (eg, financial effects of a divorce).

Conner  KM  et al. Mini-SPIN: a brief screening assessment for generalized social anxiety disorder. Depress Anxiety. 2001:14(2):139.
Spitzer  RL  et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–1097.


Complications of Injecting Drug Use

  • Local problems—Abscess (Figures 240-2 
    Image not available.

    A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

    and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
    • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
    • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
  • IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
    • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.


Content 3

Content 13

Content 11


Question 1 of 1

A 42-year-old African-American man has been diagnosed with hypertension for the past 10 years and treated with medication. One morning, he is found unresponsive by his wife. He is taken to the emergency department and pronounced dead by the physician. An autopsy revealed cardiac hypertrophy and a narrowing of the aorta just distal to the ligamentum arteriosum, with dilation of the intercostal artery's ostia. How could the death have possibly been prevented?



USMLE Reviewer (Subscription Required)