Anxiety

Signs and Symptoms

Anxiety disorders encompass excessive anxiety, which is based on the experience of fear, shared with other animals. Fear is the behavior under external, imminent danger: the body experiences a surge of adrenaline in situations requiring escape or defense of oneself, leading to the arousal state of “fight or flight”. Anxiety is the anticipation of future threat, which is an internal stimulus. It can occur in the absence of an identifiable external threat, thus responding only to an internal stimulus. It is an affect characterized by hypervigilance, muscle tension, cautious behavior and avoidance behaviors.

Anxiety that causes significant distress or disability is only normal when it occurs under an extremely stressful situation and is short-lived. Otherwise, when there is not present a substantially stressful situation or when the anxiety continues despite the stressor diminishing, an anxiety disorder is probably present.

Panic attacks are abrupt surges of intense fear or intense discomfort that reach a peak within minutes, accompanied by physical and/or cognitive symptoms. A panic attack is an abrupt surge of intense anxiety in which at least 4 of the following symptoms are experienced:

  • Palpitations, pounding heart, or accelerated heart rate
  • Sweating
  • Trembling or shaking
  • Sensations of shortness of breath or smothering
  • Feelings of choking
  • Chest pain or discomfort
  • Nausea or abdominal distress
  • Feeling dizzy, unsteady, light-headed, or faint
  • Chills or heat sensations.
  • Paresthesias (numbness or tingling sensations)
  • Derealization (feelings of unreality) or depersonalization (being detached from oneself)
  • Fear of losing control or “going crazy.”
  • Fear of dying.

Panic attacks may be expected, such as in response to a typically feared object or situation, or unexpected, meaning that the panic attack occurs for no apparent reason.

Panic Attack Disorder

Panic disorder is a type of anxiety usually emerges in a patient’s twenties and early thirties, characterized by multiple panic attacks and fear of the recurrence of them. While panic disorder has less than 10% prevalence in the population, panic attacks themselves across many psychiatric disorders and are not limited to the anxiety disorders (e.g., substance use, depressive and psychotic disorders). Panic attacks are a symptom that indicate the severity of diagnosis, course, and comorbidity across many psychiatric disorders

In panic disorder, the individual experiences recurrent unexpected panic attacks and is persistently concerned or worried about having more panic attacks or their consequences (e.g., losing control, having a heart attack, “going crazy”). There are subsequent changes his or her behavior in maladaptive ways because of the panic attacks (e.g., avoidance of exercise or of unfamiliar locationss, or leaving home entirely).

Generalized Anxiety Disorder

By far, the type of anxiety that I treat the most of is Generalized Anxiety Disorder. In this disorder, there is excessive anxiety and worry, occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance). The patient finds it difficult to control the anxiety and at least 6 of the following symptoms are experienced:

  • Restlessness or feeling keyed up or on edge
  • Being easily fatigued
  • Difficulty concentrating or mind going blank
  • Irritability
  • Muscle tension
  • Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep).

Separation Anxiety Disorder

Prior to the publication of the latest diagnostic manual in psychiatry, the DSM-5, in 2013, separation anxiety disorder had been included in the section “Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence.” However, with DSM-5, it has been placed into the “Anxiety Disorders” section. This change implies that Separation Anxiety Disorder can be diagnosed as having an onset in adults.

SepAD is exemplified by developmentally inappropriate and excessive anxiety occurring upon separation (or threat of separation) from significant attachment figures (usually parental figures). In children, this is manifested by excessive crying, tantrums, physical complaints, and other manifestations of fear and avoidance of separation. SepAD is the appropriate diagnosis in many cases of “school phobia”; the other common explanatory diagnosis is social anxiety disorder.

Older children can usually explain their fearfulness that something bad will happen to the parents if they are separated. In adults, the worries about separation from significant others and and about harm befalling them are central to their complaint, though often the pattern of behavior can be so long-standing and ingrained—since childhood—that both the patient and the significant other may rationalize the behaviors. The presentation in adulthood can be one of one of extreme dependence, in which case the diagnosis of dependent personality disorder may be applied apply.

Selective Mutism

Like separation anxiety disorder, selective mutism a disorder that was previously categorized under the section “Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence” in previous versions of the DSM. In 2013, with the DSM 5, it was moved to the “Anxiety Disorders” section. Is characterized by the failure of the individual (almost almost a child) to speak in nearly all social situations, despite apparently normal language development and abilities, as evidenced by speech with familiar people (usually the parents). Onset is in early childhood; however, precise age-at-onset data are not available, nor are good epidemiological data on the prevalence of selective mutism (although it is considered to be relatively uncommon, affecting approximately 1 in 1,000 children according to some estimates) (Bergman et al. 2002).

Most children with selective mutism are socially anxious and, in fact, meet diagnostic criteria for SAD. This has led most clinical investigators to consider selective mutism as an early-onset, severe subtype of SAD (Bögels et al. 2010; Carbone et al. 2010; Cohan et al. 2006), and in fact, at one point in the development of DSM-5, there was discussion about classifying selective mutism as such (i.e., a subtype of SAD).

Specific Phobia

A specific phobia is the marked fear or anxiety about a specific object or situation. It must be persistent (on exposure or imagined exposure to the object or situation), the fear or anxiety must be intense or severe (sometimes taking the form of a panic attack), and the individual must either be routinely taking steps to actively avoid the situation or object or be intensely distressed in its presence.

As is the case for all phobias, the fear and/or avoidance in specific phobias must be disproportionate to the actual danger posed by the situation (Craske et al. 2009). This is important because people without the specific phobia may still fear the object but not go to extraordinary lengths to avoid it or would tolerate it. For example, people with snake phobias are so frightened by the prospect of encountering a snake that they may refuse to ever go hiking, to go for walks in the park, and even to look at pictures of snakes. People with fear of hypodermic needles may refuse to have blood draws done on them despite a clear medical need to have them. Individuals with this blood-injection-injury specific phobia often demonstrate a vasovagal fainting or near-fainting response; this is one of those rare instances where patients with anxiety disorders can actually “pass out,”

Social Anxiety Disorder

Social anxiety disorder, also known as social phobia, is a condition marked by fear of social and performance situations that typically leads to avoidance. The worry is that the individual will say or do something that will result in embarrassment or humiliation. Thus, the core fear is that of negative evaluation from others. There is an underlying belief that in situations where evaluation is possible, the individual will be judged poorly and not measure up to what is expected.

As with many other anxiety disorders, SAD often occurs early in life, sometimes even before the teen years. It is also frequently comorbid (occurs together with) major depression; in young adults, is a risk factor for depression. It also has a high comorbidity with physical health conditions (Sareen et al. 2006). This comorbidity results in a high burden of functional disability that includes decreased workplace productivity, increased financial costs, and reduced health-related quality of life (Sareen et al. 2006; Stein et al. 2011a).

Clinical Course and Prognosis

Studies show that there are a set of risk factors that are common to all of the anxiety disorders. Like most depressive disorders, most anxiety disorders occur more frequently in females than in males (approximately 2:1 ratio). Younger age, single or divorced marital status, low socioeconomic status, poor social supports, and low education are associated with an increased likelihood of anxiety disorders. Whites are more likely to have anxiety disorders than ethnic minorities. Stressful life events and childhood maltreatment are also strong risk factors for anxiety disorders.

Some of the anxiety disorders typically develop in teenage years (separation anxiety disorder, specific phobia, social anxiety and agoraphobia), while others develop in the twenties and early thirties (panic disorder, generalized anxiety disorder) and tend to persist if not treated.

Prevalence and Public Health Impact

Anxiety disorders are probably the most common of mental disorders to come across the psychiatrist’s office, encompassing 40% of new referrals. In primary care setting, they make up 10%-15% of patients compared to depressive disorders making up 7%-10% of patients. They are in fact the most prevalent conditions in any age category. They are associated with substantial cost to society due to disability and loss of work productivity. Recent evidence shows that anxiety disorders are also associated with increased risk of suicidal behavior (Sareen 2011)

It is estimated that 34% of the population will be afflicted by an anxiety disorder. the phobias—particularly specific phobia and social anxiety disorder (SAD)—are the most common conditions, with specific phobia having a 15.6% lifetime prevalence and social anxiety having a 10.7% prevalence (Kessler et al. 2012). The other anxiety disorders, generalized anxiety (4.3%), panic disorder and agoraphobia (6.3%) to separation anxiety disorder (6.7%) are less prevalent.

An important thing to understand about anxiety disorders are that they are highly comorbid (meaning they occur simultaneously) with other mental disorders, personality disorders, and physical health conditions, with over 90% of persons with an anxiety disorder having lifetime comorbidity with one or more of these disorders (El-Gabalawy et al. 2013). In the presence of other conditions, the treatment of anxiety results in poorer outcomes. The most common comorbidity is the presence of another anxiety disorder. Mood and substance use (including nicotine and alcohol) disorders also commonly co-occur with anxiety disorders. Because anxiety disorders often precede the onset of mood disorders and substance use, early interventions to treat anxiety disorders may prevent mood and substance use disorders. Anxiety disorders are also commonly comorbid with personality disorders, such as borderline, antisocial, and avoidant personality disorders (El-Gabalawy et al. 2013).

Physical health conditions are also common among patients with anxiety disorders (Sareen et al. 2006). Among the comorbid physical health conditions, the most prevalent are cardiovascular disease, respiratory illness (e.g., asthma), arthritis, and migraines. The onset of a serious physical illness might trigger the onset of an anxiety disorder, or conversely, anxiety and avoidance might lead to physical health problems.

Research

Inheritance

Among genetic and family factors, there is increasing evidence for the familial transmission of anxiety disorders through both genetic transmission and modeling. With panic disorder, generalized anxiety disorder, and social anxiety disorder, research has supported a “stress-diathesis” model, explaining risk as a predispositional vulnerability together combined with stress from life experiences. Studies have suggested that early life trauma or maltreatment (Stein et al. 1996) is an important risk factor, extending to both anxiety and depressive disorders. Twin studies suggest that panic disorder has moderate heritability (~ 40%) (Gelernter and Stein 2009). From a genetic perspective, it is believed that anxiety disorders are complex disorders with multiple genes conferring vulnerability through as-yet largely undetermined pathways (Manolio et al. 2009; Smoller et al. 2009).
Some other promising leads have emerged (Logue et al. 2012). For example, several studies have implicated the adenosine 2A receptor gene (ADORA2A) as having a possible role in panic disorder, consistent with the anxiogenic effects of caffeine, a known antagonist at this receptor (Hohoff et al. 2010). Association studies examining genes involved in other neurotransmitter systems thought to be associated with fear and anxiety (e.g., norepinephrine and serotonin) have produced inconsistent, often non-replicated results. The most consistent results have involved the 22q11 catechol O-methyltransferase gene (COMT) that codes for the enzyme responsible for norepinephrine metabolism.

Learning theory

Beginning in 1967 with Pitt’s observation that sodium lactate provoked panic attacks in patients with panic disorder but not in control subjects (Pitts and McClure 1967), a series of studies showed that agents with disparate mechanisms of action such as caffeine, isoproterenol, yohimbine, carbon dioxide, and cholecystokinin (CCK) had similar abilities to provoke panic in patients with panic disorder but not in control subjects (Roy-Byrne et al. 2006). Many of these neurobiological “challenge” agents have been thought to have specific effects on the brain’s fear circuits, which are believed to function aberrantly in patients with panic disorder. The studies of these challenge agents were originally proposed to indicate specific biochemical abnormalities in panic disorder. However, many investigators now agree that most of the effects elicited by these compounds can be explained on the basis of learning theories of panic disorder, which emphasize that patients with panic disorder misinterpret and are frightened by perceived perturbations in their physiological state.

Elevated anxiety-sensitivity is probably multi-factorial, studies suggesting that it may be acquired from recurrent direct aversive experience such as maltreatment in childhood or physical suffering during illness such as asthma, vicarious observations (e.g. significant illnesses or deaths among family members), or parental reinforcement or modeling of distressed reactions to bodily sensations. This factor may contribute to a heightened state of interoceptive attention (attention to internal sensations) that primes the individual to experience panic attacks and to be intensely frightened by them when they occur. Hence, “fear of fear” develops after the initial panic attacks results in interoceptive conditioning (conditioned fear of internal cues such as pounding heart and shortness of breath) and the subsequent interpretation of these internal cues as indicating something dangerous (e.g., loss of control, heart attck, or stroke), thus further causing strengthening of these cues. (Bouton et al. 2001).

Neuroanatomy

Alterations in the functioning of fear circuitry are generally posited across many of the anxiety disorders, with dysfunction in the amygdala and its connections believed to play an important etiological role in the pathophysiology of an array of fear-based disorders, including panic disorder, social phobia, and PTSD (Etkin and Wager 2007; Figure 5-). Amygdala dysfunction may also be a critical underlying factor in anxiety proneness more generally (Stein et al. 2007). Functional neuroimaging data suggest that a particular brain structure, the insula, is involved in the intense awareness of somatic sensations experienced by patients with panic disorder and related disorders (Paulus and Stein 2010).

SAD seems to involve abnormal responding in anxiety circuitry that includes the amygdala and insular cortex, findings that are shared with several other anxiety and trauma-related disorders (Etkin and Wager 2007). Adults with SAD demonstrate a variety of attentional, interpretative, and other cognitive biases (Ouimet et al. 2009), the origins of which are poorly understood but which nonetheless may be a focus for therapeutic interventions, such as those discussed later in this chapter.

Tempermental Factors

Some specific phobias develop following a traumatic event (e.g., being bitten by a dog), but most patients with specific phobia do not recall any experiential precursor (e.g., most snake phobics have never been bitten by a snake and most flying phobics have never been in a plane crash). Temperamental factors that are a risk factor for specific phobia, such as neuroticism or behavioral inhibition, are shared with other anxiety disorders (Craske et al. 2009).

Treatment for Anxiety

Anxiety disorders tend to respond well to psychological and pharmacological treatments, but the initial assessment is important in order to spell out the direction of the treatment.
The impact on functioning and the suicidal risk are key elements that will guide the intensity or speed of the treatment.

Next, there next to be a consideration of the differential diagnoses (the other possible diagnoses and causes for the symptoms). These can include substance-indeed anxiety or medical condition related anxiety. Along these lines, there should be a physical done and laboratory exams performed.

Following that, there should be an identification of the type of anxiety(ies) that are involved in the individual’s symptoms. (e.g. separation anxiety disorder, selective mutism, social anxiety disorder, panic disorder, generalized anxiety disorder, specific phobia, agoraphobia).

There also needs to be considered whether the patient has other mental disorders, such as a depressive disorder, which is often comborbid with an anxiety disorder.

Finally, there needs to be psychoeducation of the patient, leading to consideration for psychotherapy as well as pharmacological therapy.

Psychotherapy

Cognitive Behavioral Therapy starts with understanding the behavioral model of anxiety, which suggests that individuals respond to external and internal triggers that lead to a sense of danger. The sense of danger leads to a fight-or-flight response and they avoid the triggering situation. Behavioral treatments of anxiety disorders aim to expose the individual to the anxiety-provoking situation and prevent the response of avoidance. Through systematic desensitization, patients gradually but in increasingly more challenging situations face the phobic stimuli that make them feel anxious.

At the core of CBT are the four components: psychoeducation, relaxation training, cognitive restructuring, and exposure therapy. Among the psychosocial interventions for anxiety disorders, CBT has the most robust evidence for efficacy.

As an example, a particular patient may have panic attacks that are triggered by isolated chest pains. These chest pains lead the anxiety-provoking thought that she could be having a heart attack. The patient would learn ways to challenge this thinking through looking at evidence for and against the thought that she is having a heart attack, thus restructuring her cognition.

Exposure therapy would then be used with this patient to reinforce this restructuring; exposure therapy for panic disorder often involves exercises that recreate the panic symptoms (interoceptive exposure). One technique often used to recreate these symptoms is hyperventilation, because this phenomenon is common in panic attacks. When used as a technique in exposure therapy, the patient and the therapist hyperventilate together for brief periods and patients are taught that the physiological symptoms will resolve on their own.

Next, the patient would be asked to make a hierarchical list of situations that she avoids because of anxiety. Over the course of the therapy the patient would slowly face the anxiety-provoking situations and learn that if she stays in the situation long enough, the anxiety resolves.

Other techniques that CBT include to promote relaxation training are deep muscle relaxation and/or breathing management.

CBT techniques can be very empowering for patients. They often feel alone and bewildered, especially if they have not known other who have had anxiety symptoms like their own. The sharing of unbiased high-quality information can greatly lessen this sense of being isolated. Information is available at the Web sites of the National Institutes of Health (www.nih.gov), Anxiety and Depression Association of America (www.adaa.org), or UpToDate (www.uptodate.com; provides free access to medical information in materials written expressly for consumers), among others.

Pharmacotherapy

Pharmacotherapy is a good option for many patients with anxiety disorders, either in combination with cognitive behavior therapy or as a stand-alone treatment. The main medications used for anxiety disorders are the antidepressants and the benzodiazepine anxiolytics. The antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). On occasion, there are several nonbenzodiazepine anxiolytics (e.g., buspirone and pregabalin) and atypical antipsychotics (for refractory anxiety) that are used. Antidepressants are more thoroughly discussed in the antidepressant section of the depression page of this blog.

References

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Bögels SM, Alden L, Beidel DC, et al: Social anxiety disorder: questions and answers for the DSM-V. Depress Anxiety 27:168–189, 2010

Bouton ME, Mineka S, Barlow DH: A modern learning theory perspective on the etiology of panic disorder. Psychol Rev 108:4–32, 2001

Carbone D, Schmidt LA, Cunningham CC, et al: Behavioral and socio-emotional functioning in children with selective mutism: a comparison with anxious and typically developing children across multiple informants. J Abnorm Child Psychol 38:1057–1067, 2010

Cohan SL, Price JM, Stein MB: Suffering in silence: why a developmental psychopathology perspective on selective mutism is needed. J Dev Behav Pediatr 27:341–355, 2006

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Craske MG, Stein MB, Sullivan G, et al: Disorder-specific impact of coordinated anxiety learning and management treatment for anxiety disorders in primary care. Arch Gen Psychiatry 68:378–388, 2011

El-Gabalawy R, Tsai J, Harpaz-Rotem I, et al: Predominant typologies of psychopathology in the United States: a latent class analysis. J Psychiatr Res 47:1649–1657, 2013

Etkin A, Wager TD: Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 164:1476–1488, 2007

Kessler RC, Petukhova M, Sampson NA, et al: Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 21:169–184, 2012

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Stein MB, Simmons AN, Feinstein JS, et al: Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am J Psychiatry 164:318–327, 2007