Panic Disorder

Panic attacks are defined as discrete periods of intense fear or discomfort that begin abruptly and reach their peak within 10 minutes. The DSM-5 requires that at least 4 of the following 13 symptoms be present: 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, lightheaded, or faint; derealization or depersonalization; fear of losing control or going crazy; fear of dying; paresthesias; and chills or hot flushes. Panic attacks occur in nonclinical populations, with about 6.3% of a community sample reporting having experienced a full-blown panic attack some time during their lives (Norton, Zvolensky, Bonn-Miller, Cox, & Norton, 2008) without debilitating consequences, development of a disorder, or treatment-seeking behavior.

Panic attacks also occur in the context of many psychiatric conditions, especially anxiety disorders. For example, the acute fear responses that individuals with specific phobias experience in the presence of feared objects or situations (e.g., spider phobics’ responses to spiders) sometimes meet the criteria for a panic attack. When a panic attack is triggered by exposure to or anticipation of a feared object or situation, it is considered to be an expected panic attack (also known as a cued panic attack). Expected panic attacks are most common among individuals with other anxiety disorders, including social anxiety disorder and specific phobias.

In addition to expected panic attacks, panic attacks can also be unexpected (or uncued); these panic attacks are not associated with any specific object or situation. Anyone, including individuals with no diagnoses, can experience expected or unexpected panic attacks. Expected panic attacks are not uncommon among individuals with social anxiety disorder or specific phobias, but they also occur in a substantial number of patients with panic disorder (Craske et al., 2010). One issue that should be considered when diagnosing panic disorder is that the term unexpected may have different meanings across various cultural contexts (Lewis-Fernández et al., 2010).

The diagnosis of panic disorder requires recurrent and unexpected (uncued) panic attacks, followed by at least 1 month of concern about (a) additional attacks or the implications of the attack, or (b) changes in behavior (APA, 2013). The DSM-5 does not recognize subtypes of panic disorder (e.g., respiratory, nocturnal, nonfearful, cognitive, and vestibular subtypes), although some investigators have recently explored the possibility of categorizing panic disorder in this way (see Kircanski, Craske, Epstein, & Wittchen, 2010).

Agoraphobia

Agoraphobia is a fear of being in public places or situations in which escape might be difficult or in which help may be unavailable if a panic attack occurred. Patients with agoraphobia avoid (or endure with marked distress) certain situations, including large stores; open or crowded public spaces; traveling on buses, trains, or cars; and being far or away from home (APA, 2013).

The DSM-III-R (APA, 1987) viewed agoraphobia as primary and panic attacks as a frequent but secondary feature. It included the diagnostic categories of “agoraphobia with panic attacks” and “agoraphobia without panic attacks.” Subsequent revisions of the DSM have reversed this view and have included diagnostic categories of “panic disorder with agoraphobia,” “panic disorder without agoraphobia,” and an infrequently used category of “agoraphobia without panic disorder.” This last category is used for patients who deny or have an unclear history of panic attacks, or who merely report histories of panic-like experiences (e.g., limited symptom panic attacks). Such cases may be difficult to differentiate from specific phobias, obsessive-compulsive disorder, and posttraumatic stress disorder. Although agoraphobia was seen as a frequent but secondary feature of panic disorder in the DSM-III-R and DSM-IV, the view that it is a distinctive condition independent of panic disorder (Wittchen, Gloster, Beesdo-Baum, Fava, & Craske, 2010) is now incorporated into the DSM-5.

Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is characterized by worry (APA, 2013), which is typically defined as repetitive thinking about potential future threat, imagined catastrophes, uncertainties, and risks (Watkins, 2008). Individuals with GAD spend an excessive amount of time worrying and feeling anxious about a variety of topics, and they find it difficult to control the worry. The diagnosis also requires three or more of the following six symptoms: (1) restlessness or feeling keyed up or on edge; (2) being easily fatigued; (3) difficulty concentrating or mind going blank; (4) irritability; (5) muscle tension; and (6) sleep disturbance. Finally, the worry and anxiety are not confined to another disorder (e.g., worry about social evaluation only in the context of social anxiety disorder), and they lead to significant distress or impairment.

The diagnosis of GAD first appeared in the DSM-III (APA, 1980), but it was poorly defined, unreliable, and assigned only in the absence of other disorders (Mennin, Heimberg, & Turk, 2004). With publication of the DSM-III-R (APA, 1987), the diagnostic criteria for GAD were revised to include worry as the primary feature and to allow for primary diagnoses of GAD in the presence of other disorders. Despite these improvements, diagnostic reliability remained poor due to overly broad criteria for associated symptoms (Marten et al., 1993). The DSM-IV (APA, 1994) added the uncontrollability criterion and reduced the set of associated symptoms to reflect empirical findings and to improve specificity. As a result, diagnostic reliability improved but remained low relative to most of the other anxiety disorders (Brown, Di Nardo, Lehman, & Campbell, 2001). The DSM-5 continues to use the same diagnostic criteria.

Although worry is the primary diagnostic and clinical feature of GAD, the majority of high worriers do not meet criteria for the disorder (Ruscio, 2002). However, compared to high worriers without GAD, high worriers with GAD report greater distress and impairment associated with worry, indicating that worry is more harmful at clinical levels. High worriers with GAD are also more likely to perceive their worry as uncontrollable (Ruscio & Borkovec, 2004). Individuals who do not meet the “excessiveness of worry” criterion may present a milder form of GAD; they are less symptomatic overall and report fewer comorbid disorders compared to individuals with full GAD (Ruscio et al., 2005). Nonetheless, GAD without “excessive” worry is associated with considerable impairment, high rates of treatment seeking, and high rates of comorbidity.

GAD was initially conceptualized as a “nonphobic anxiety disorder” and was instead classified (alongside panic disorder) under the umbrella of “anxiety neurosis” (DSM-II; APA, 1968). Although it remains unclear whether GAD is indeed a “nonphobic” condition in which no specific feared stimulus exists, several theoretical conceptualizations of GAD converge on the idea that worry serves an avoidant function. These conceptualizations include the avoidance theory, the intolerance of uncertainty model, the meta-cognitive model, and emotion regulation models (for a detailed review, see Behar, DiMarco, Hekler, Mohlman, & Staples, 2009).

The avoidance theory (Borkovec, Alcaine, & Behar, 2004) holds that the verbal-linguistic properties of worry preclude emotional processing. Worry is primarily verbal-linguistic as opposed to imagery based in nature (Behar, Zuellig, & Borkovec, 2005; Borkovec & Inz, 1990; Stöber, Tepperwien, & Staak, 2000), and it inhibits somatic arousal during a subsequent anxiety-inducing task (Borkovec & Hu, 1990; Borkovec, Lyonfields, Wiser, & Deihl, 1993; Peasley-Miklus & Vrana, 2000). Moreover, worry is associated with decreased anxious affect during subsequent periods of trauma recall (Behar et al., 2005) and depressive rumination (McLaughlin, Borkovec, & Sibrava, 2007). Lastly, individuals with GAD often report that worry serves as a distraction from more emotional topics (Borkovec & Roemer, 1995). Thus, it seems that worry precludes the somatic and emotional activation required for habituation to anxiety-provoking stimuli. Moreover, worry may be negatively reinforced via the removal of aversive and evocative images and emotional experiences (Borkovec et al., 2004).

Intolerance of uncertainty (IU) is defined as the tendency to respond negatively to uncertain situations in terms of cognition, affect, and behavior (Dugas, Buhr, & Ladouceur, 2004). IU is further defined as a schema through which an individual with GAD perceives the environment; for the individual with GAD, uncertain situations are unacceptable and distressing and may lead to worry (Dugas et al., 2004). Individuals with GAD consistently report greater levels of IU compared to nonclinical controls (Dugas, Gagnon, Ladouceur, & Freeston, 1998; Ladouceur, Blais, Freeston, & Dugas, 1998) and individuals with other anxiety disorders (Dugas, Marchand, & Ladouceur, 2005; Ladouceur et al., 1999). Finally, worry partially statistically mediates the relationship between IU and anxiety (Yook, Kim, Suh, & Lee, 2010).

The premise of the metacognitive model of GAD is that individuals with GAD experience two types of worry: Type 1 worry refers to worry about external threats and noncognitive internal triggers (e.g., physical symptoms), whereas Type 2 worry refers to meta-worry, or worry about worry (Wells, 1995, 2004). Positive beliefs about worry (e.g., that worrying will help avoid a catastrophe) give rise to Type 1 worry, whereas negative beliefs about worry (e.g., the belief that worry is uncontrollable) prompt Type 2 worry. Negative beliefs about worry may be more specific to GAD compared to positive beliefs about worry. Individuals with GAD perceive worry as more dangerous and uncontrollable than do individuals with other anxiety disorders and controls, even when controlling for Type 1 worry (Davis & Valentiner, 2000; Wells & Carter, 2001). Type 2 worry, on the other hand, may not be specific to GAD; individuals with GAD do not report greater positive beliefs about worry compared to anxious nonworriers (Davis & Valentiner, 2000), high worriers without GAD (Ruscio & Borkovec, 2004), and individuals with other anxiety disorders (Wells & Carter, 2001).

Emotion dysregulation models propose that individuals with GAD have difficulties understanding and modulating their emotions, and they may instead rely on suppression and control strategies (e.g., worry; Mennin, Heimberg, Turk, & Fresco, 2002). The model further describes specific components of emotion dysregulation in GAD, including heightened intensity of emotions (both positive and negative, but particularly negative; Turk, Heimberg, Luterek, Mennin, & Fresco, 2005), poor understanding of emotions, negative reactivity to emotions, and maladaptive management of emotions (Mennin, Heimberg, Turk, & Fresco, 2005; Mennin, Holaway, Fresco, Moore, & Heimberg, 2007). Both analogue and clinical GAD samples report higher emotion dysregulation compared to nonanxious participants, although individuals with depression report similar deficits. Moreover, self-reported emotion dysregulation predicts severity of trait worry and analogue GAD status when controlling for negative affect (Salters-Pedneault, Roemer, Tull, Rucker, & Mennin, 2006), as well as dimensional GAD-Q-IV scores when controlling for symptoms of depression and anxious arousal (Roemer et al., 2009). The acceptance-based model also posits difficulties with emotional experiences in GAD, but instead focuses on fear and avoidance of internal experiences (Roemer, Salters, Raffa, & Orsillo, 2005). Indeed, deficits in mindfulness account for unique variance in GAD symptom severity, even after controlling for emotion regulation and depressive and anxious symptoms (Roemer et al., 2009).

Social Anxiety Disorder

Social anxiety disorder, sometimes referred to as social phobia, is a marked and persistent fear of social or performance situations in which embarrassment may occur. Exposure to or anticipation of the feared social situation almost invariably provokes anxiety or fear. Acute fear responses can take the form of situationally bound or predisposed panic attacks. Feared situations include performing certain activities in the presence of others (such as speaking, eating, drinking, or writing), or fearing that one may do something that will cause humiliation or embarrassment, such as saying something stupid or not knowing what to say, behaving inappropriately, or appearing overly anxious. The diagnosis requires that these feared situations are either avoided or endured with significant distress (APA, 2013). The insight criterion found in prior versions of the DSM (i.e., that the individual recognizes that the fear is irrational) has been replaced with the criterion that the clinician judges the fear to be out of proportion to actual danger (APA, 2013). Cultural factors are likely to affect the assessment of this requirement, as it implies a comparison to the patient’s social reference group (Lewis-Fernández et al., 2010).

If an individual fears many or most social interactions, the generalized subtype should be specified. Generalized social anxiety disorder overlaps considerably with avoidant personality disorder, “so much so that they may be alternative conceptualizations of the same or similar conditions” (APA, 2000, p. 720). Individuals not assigned to the generalized subtype are commonly viewed as belonging to a nongeneralized or specific subtype. Compared to the nongeneralized subtype, the generalized subtype is associated with greater comorbidity, earlier age of onset, and greater heritability, and is generally an indicator of greater severity, as is the overlapping diagnosis of avoidant personality disorder (Bögels et al., 2010).

Social anxiety disorder may subsume three other possible disorders. First, the separate diagnostic category of selective mutism may be an expression of social anxiety disorder during childhood (Bögels et al., 2010). This conceptualization of selective mutism treats the refusal to talk as a form of social avoidance. Second, the DSM-5 recognizes a culturally bound syndrome, Taijin Kyofusho, found mainly in Japan and Korea. The Korean term Taein-kongpo is used interchangeably with social anxiety disorder (Kim, personal communication, 2010). These conditions appear to be the same as anthropophobia, a condition recognized in the ICD-10 (World Health Organization, 1992). These conditions involve a fear of offending and making others uncomfortable, such as through poor manners or bad odors, and have also been documented in Western cultures (Kim, Rapee, & Gaston, 2008; McNally, Cassiday, & Calamari, 1990). Lewis-Fernández et al. (2010) have suggested that the definition of social anxiety disorder could be broadened to subsume Taijin Kyofusho and equivalent conditions. Third, the DSM-5 does not recognize test anxiety as a separate disorder but subsumes it within social anxiety disorder. LeBeau et al. (2010) suggested that one form of test anxiety may be a form of social anxiety disorder in that it involves social evaluative concerns and acute fear reactions, whereas a second form may be a form of generalized anxiety disorder in that it involves anticipatory anxiety and worry. The DSM-5 requires a specification when “performance anxiety only” applies, implying that there may be two distinct conditions within the diagnostic category of social anxiety disorder.

Specific Phobias

Specific phobias are marked and persistent fears of clearly discernible, circumscribed objects or situations. Exposure or anticipation of exposure to the feared object or situation almost invariably provokes anxiety or fear. Acute fear responses can take the form of expected (situationally bound or cued) panic attacks. Five subtypes of specific phobia are recognized by the DSM-5 and are specified based on the type of object or situation that is feared: animals (e.g., dogs, snakes, spiders), natural environment (e.g., storms, water, heights), blood-injection-injury (BII; e.g., seeing blood, getting an injection with a syringe), situations (e.g., elevators, flying), and other (e.g., situations related to choking, vomiting, illness, falling without means of physical support). The diagnosis requires that these feared situations are either avoided or endured with significant distress (APA, 2013).

Although many individuals meet criteria for a specific phobia, very few seek treatment (Barlow, DiNardo, Vermilyea, Vermilyea, & Blanchard, 1986), although individuals with comorbid diagnoses might be more likely to seek treatment (Barlow, 1988). Animal phobia and height phobia are the most frequently diagnosed forms (Curtis, Magee, Eaton, Wittchen, & Kessler, 1998; Stinson et al., 2007). Although subtypes of specific phobia appear to have relatively distinctive ages of onset (Öst, 1987), they are generally accepted as constituting a single category. An exception is that the BII subtype may be or may subsume a disorder with distinct features and etiological factors (LeBeau et al., 2010; Page, 1994).

Diagnostic Considerations

Anxiety disorders identified in the DSM-5 show considerable overlap and high rates of comorbidity. These observations suggest that a categorical approach to understanding these problems is not optimal. In addition, these problems do not appear to be discontinuous from normal (nonclinical) variation. Dimensional methods may more accurately model the nature of these problems (Krueger, 1999; Watson, 2005) and may eventually come into use. Given the usefulness of the diagnostic categories of panic disorder, GAD, social anxiety disorder, and specific phobias, it is not surprising that the definitions of these diagnoses have not changed substantially since the publication of the DSM-III-R.

One model for organizing internalizing problems involves distinguishing between distress and fear disorders (Krueger, 1999; Watson, 2005). Panic disorder and specific phobias involve acute fear reactions and avoidance behaviors that occur in response to specific stimuli. In panic disorder, the feared stimulus is an internal physiological sensation, such as a racing heart or dizziness. Each subtype of specific phobia is cued by a class of feared stimuli (e.g., snakes, heights). These fear disorders can be distinguished from distress disorders that include major depressive disorder, GAD, and other internalizing disorders not characterized by an acute fear response.

The anxiety associated with GAD does not appear to occur in response to specific feared stimuli, but rather can be thought of as “anxious expectation” (APA, 2013). Elsewhere it has been described as “a chain of thoughts and images, negatively affect-laden and relatively uncontrollable; it is an attempt to engage in mental problem-solving on an issue whose outcome is uncertain but contains the possibility of one or more negative outcomes” (Borkovec, Robinson, Pruzinsky, & DePree, 1983; p. 10). Interpersonal concerns are the most commonly reported worry topic, regardless of GAD status (Roemer, Molina, & Borkovec, 1997). However, individuals with GAD are more likely than those without GAD to worry about minor or routine issues, as well as health or illness (Craske, Rapee, Jackel, & Barlow, 1989; Roemer, Molina, Litz, & Borkovec, 1997). They also report more worry topics overall and that their worry is less controllable and more realistic. Finally, although the diagnosis of GAD is categorical, taxometric analyses have indicated that worry exists on a continuum and may occur to a greater or lesser extent in a given individual (Olatunji, Broman-Fulks, Bergman, Green, & Zlomke, 2010; Ruscio, Borkovec, & Ruscio, 2001). Given that worry is the core diagnostic feature of GAD, these findings support a dimensional classification of the disorder.

Although many of the physiological symptoms of GAD overlap with depression, the DSM-5 criteria for GAD include those symptoms that show unique associations with worry after controlling for depression. These symptoms include muscle tension (Joormann & Stöber, 1999), gastrointestinal symptoms, and aches and pains (Aldao, Mennin, Linardatos, & Fresco, 2010).

Watson (2005) found that social anxiety disorder shows closer relationships with depression and GAD than it does with panic disorder, suggesting that it might be conceptualized as a distress disorder. However, for the nongeneralized subtype, acute fear reactions (including cued panic attacks) are often triggered by social situations, such as having to give a speech to an audience. Thus, generalized social anxiety disorder may be a distress disorder, whereas the nongeneralized subtype may be a fear disorder (Carter & Wu, 2010).

Although the DSM-5 does not recognize higher-order classes of distress and fear disorders, there is good evidence for these superordinate classes because of patterns of comorbidity or co-occurrence of symptoms and patterns of shared heritable risk (Krueger, 1999). Presence (versus absence) of an acute fear response and avoidance behavior may be the key diagnostic distinction for fear disorders (versus distress disorders). Differential diagnosis within the fear disorder category (e.g., panic disorder versus animal phobia versus natural environment phobia) requires identification of the feared stimuli. For example, if panic attacks only occur upon exposure to or anticipation of a specific stimulus, then panic disorder is not indicated and the specific stimulus provides a clue as to the subtype of specific phobia that best describes the condition.

Despite such questions about the best way to conceptualize these types of problems, the DSM-5 categories have proven to be quite useful, especially with regard to predicting prognosis and treatment response. These disorders are quite recognizable, with relatively good reliability of diagnosis when using a semistructured interview (Brown, Campbell, Lehman, Grisham, & Mancill, 2001). Additionally, given the availability of a host of treatment manuals, treatment planning is greatly facilitated when working with patients seeking treatment for panic disorder, GAD, social anxiety disorder, or specific phobias. Finally, it should be noted that anxiety disorders present risk of suicide, especially when comorbid diagnoses (e.g., depression, personality disorders) are present (Cox, Direnfeld, Swinson, & Norton, 1994; Khan, Leventhal, Khan, & Brown, 2002; Warshaw, Dolan, & Keller, 2000).

Panic Disorder

Generalized Anxiety Disorder

Social Anxiety Disorder

Specific Phobia

Pharmacological Treatments

Cognitive-Behavioral Treatments

Other Psychological Treatments

Acceptance and commitment therapy (ACT; Hayes, Luoma, Bond, Masuda, & Lillis, 2006) is another psychological treatment for anxiety disorders that has garnered recent interest. Broadly speaking, ACT seeks to reduce the extent to which individuals respond to thoughts and other inner experiences in ways that maintain and exacerbate emotional distress. Preliminary data indicate that ACT is an efficacious treatment for reducing anxiety symptoms (e.g., see Öst, 2008). Moreover, ACT-based treatments for panic disorder (Lopez & Salas, 2009) and social anxiety disorder (Dalrymple & Herbert, 2007) have been examined.

Mindfulness-based approaches have also received attention recently, particularly in the treatment of GAD. Mindfulness is defined as “paying attention in a particular way, on purpose, in the present moment, and nonjudgmentally” (Kabat-Zinn, 1994, p. 4) and “bringing one’s complete attention to the present experience on a moment-to-moment basis” (Marlatt & Kristeller, 1999, p. 68). Thus, mindfulness-based treatments for GAD aim to increase clients’ awareness and acceptance through practicing mindfulness of internal and external experiences, nonjudgmental observation of those experiences, relaxation, meditation, and a focus on the present moment (Roemer, Salters-Pedneault, & Orsillo, 2006). Mindfulness-based interventions have been shown to be efficacious as stand-alone treatments (e.g., Roemer, Orsillo, & Salters-Pedneault, 2008), and can also be added to traditional CBT techniques (Behar, Goldwin, & Borkovec, in press) in an attempt to increase efficacy.

Other psychological treatments that have garnered some interest in the treatment of panic disorder, GAD, social anxiety disorder, and specific phobias include interpersonal therapy, psychoanalytic psychotherapy, and eye movement desensitization and reprocessing (EMDR) therapy. High-quality randomized and controlled clinical trials have generally not yet been conducted, or have found no support for treating these disorders with these alternate psychological approaches. For example, an examination of the efficacy of EMDR in the treatment of panic disorder with agoraphobia indicated that EMDR was not significantly different from a credible attention placebo condition (e.g., Goldstein, de Beurs, Chambless, & Wilson, 2000). These treatments are, therefore, not widely considered to be first-line treatments (Hamm, 2009; Jorstad-Stein & Heimberg, 2009; McHugh et al., 2009).

Combined Pharmacological and Psychological Treatments

Predictors of Treatment Outcome

A host of variables may predict enhanced or compromised response to treatment across anxiety disorders. One commonly examined predictor of treatment outcome is symptom severity. In panic disorder, higher levels of agoraphobia are associated with poorer treatment outcome (e.g., Cowley, Flick, & Roy-Byrne, 1996; Warshaw, Massion, Shea, Allsworth, & Keller, 1997). However, in GAD, the evidence is mixed. Some investigations have shown that patients with more severe anxiety at pretreatment respond less well to therapy (Butler, 1993; Butler & Anastasiades, 1988; Yonkers, Dyck, Warshaw, & Keller, 2000), whereas others have failed to find such relationships (e.g., Barlow, Rapee, & Brown, 1992; Biswas & Chattopadhyay, 2001; Durham, Allan, & Hackett, 1997). In social anxiety disorder, greater severity of depression and greater severity of avoidant personality traits are related to poorer treatment outcome (Chambless, Tran, & Glass, 1997).

Overall, there are mixed findings regarding the impact of comorbid conditions on treatment outcome. For example, some research indicates that individuals with panic disorder who have comorbid major depressive disorder evidence poorer treatment outcome (Cowley et al., 1996), whereas other research has found that such comorbidity does not negatively impact treatment outcome in panic (McLean, Woody, Taylor, & Koch, 1998; Tsao, Mystkowski, Zucker, & Craske, 2002). In GAD, the presence of a comorbid Axis I disorder generally (Durham et al., 1997), and comorbid dysthymia or panic disorder specifically (Tyrer, Seivewright, Simmonds, & Johnson, 2001), predict relapse of symptoms. In specific phobias, the presence of additional comorbid anxiety disorders does not seem to affect treatment outcome (Ollendick, Öst, Reuterskiöld, & Costa, 2010).

Interpersonal problems seem to predict a poor response to treatment among individuals with GAD patients. For example, Borkovec et al. (2002) found that interpersonal problems remaining at treatment termination predicted poorer functioning at post-therapy and follow-up assessments. Likewise, personality disorder traits are associated with poorer response to cognitive therapy and self-help treatments among GAD patients (Tyrer, Seivewright, Ferguson, Murphy, & Johnson, 1993).

Finally, several treatment process variables (e.g., therapeutic alliance, treatment compliance) have also been examined as predictors of treatment outcome. The degree to which patients expect to change seems to be especially important (Jorstad-Stein & Heimberg, 2009). For example, research indicates that lower levels of treatment expectancy are related to poorer outcome in social anxiety disorder (Chambless et al., 1997).

Behavioral Genetics

Behavioral genetic studies (e.g., studies of identical twins, studies of adopted siblings) estimate that about 20% of the variance in panic disorder, social anxiety disorder, and specific phobias is attributable to genetic factors (e.g., Hettema, Neale, Myers, Prescott, & Kendler, 2006). Familial factors (i.e. environmental factors shared by twins and siblings) account for less than 10% of the variance in the occurrence of the disorders, and the majority of the variance (perhaps as much as 70%) is attributed to unique environmental factors and measurement error. Although some behavioral genetics studies have resulted in higher estimates of the contribution of heritable genetics (perhaps as high as about 50% when correcting for measurement error; Kendler, Karkowski, & Prescott, 1999; Kendler, Myers, Prescott, & Neale, 2001), it is generally agreed that compared to most other psychological conditions, these anxiety disorders appear to be relatively less influenced by heritable genetics and more influenced by environment or by gene-environment interactions. A notable exception to these findings is that the BII subtype of specific phobia appears to be relatively more heritable (Kendler et al., 1999, 2001). In addition, when social anxiety disorder subtypes are examined, the generalized subtype appears to involve somewhat greater heritable genetic risk than the nongeneralized subtype (Mannuzza et al., 1995; Stein et al., 1998).

Some of the heritable genetic risk for panic disorder and specific phobias appears to be due to a general factor (perhaps neuroticism; Gray & McNaughton, 2000; Hettema et al., 2006) underlying most internalizing disorders (Krueger, 1999). A substantial part of the heritable genetic risk is specific to the group of disorders that involves acute fear reactions (Krueger, 1999). A modest amount of disorder-specific heritable genetic risk has been found for panic disorder (Hettema et al., 2006). It is also noteworthy that anxiety sensitivity (Stein, Lang, & Livesley, 1999), which is a risk factor for panic disorder (see Personality and Temperament: Anxiety Sensitivity), and behavioral inhibition (Hirschfield-Becker, Biederman, & Rosenbaum, 2004), which is a risk factor for social anxiety disorder (see Personality and Temperament: Behavioral Inhibition and Shy Temperament), are heritable. Although the largest portion of heritable genetic risk appears to involve a general factor underlying the entire class of disorders that involve acute fear reactions, unique environmental factors appear to play a considerable role, particularly with regard to which type of acute fear disorder develops.

A meta-analysis of family and twin studies found that genetic factors account for approximately 32% of the variance in liability to GAD (Hettema, Neale, & Kendler, 2001). Not surprisingly, there is considerable overlap in genetic liability for GAD and major depressive disorder, 25% of which is accounted for by neuroticism (Kendler, Gardner, Gatz, & Pedersen, 2007). Furthermore, a large twin study found that GAD and depression were linked to one genetic factor termed “anxious-misery,” whereas the phobias were linked to another factor termed “fear” (panic disorder was linked to both factors, but less strongly; Kendler, Prescott, Myers, & Neale, 2003). A similar study examining only anxiety disorders found that GAD is linked to the same genetic factor as panic disorder and agoraphobia, whereas a different genetic factor was associated with situational and animal phobias (Hettema, Prescott, Myers, Neale, & Kendler, 2005). Despite genetic overlap, family studies suggest that GAD and panic disorder are somewhat distinct. For example, rates of GAD are higher among relatives of individuals with GAD compared to relatives of individuals with panic disorder (Noyes et al., 1992; Weissman, 1990).

Biological Considerations

The neuroanatomy, neurochemistry, and endocrinology underlying normal fear processes have been studied extensively (see Meaney, LeDoux, & Liebowitz, 2008). Normal fear and panic responses are often understood as part of a complex physical system involving neural, endocrinological, circulatory, muscular, and behavioral systems. This fight-or-flight system is designed to prevent or avoid physical danger and harm, and involves a fast and efficient response. Perceptions of immediate danger trigger a cascade of physical reactions that begin in the amygdala, which projects to the hypothalamus. The hypothalamus releases corticotropin-releasing factor (CRF), which triggers the pituitary to release adrenocorticotropic hormone (ACTH), which in turn triggers the adrenal cortex to release hormones, including cortisol. These hormones play a central role in regulating the body’s preparation for stress.

The hypothalamus also activates the sympathetic nervous system, resulting in a variety of bodily changes including the release of glucose from the liver; increases in heart rate, breathing, and blood pressure; a pattern of vasodilation and vasoconstriction that increases blood flow to the major muscles; and other changes associated with preparation for the fight-or-flight response.

These physiological changes constitute the physical symptoms of panic attacks. Numbing and tingling in the fingers and toes and sensations in the stomach (nausea) and bladder are sometimes experienced as less blood reaches these nonvital areas; shaking and trembling are by-products of the readiness of the major muscles to expend energy; sweating is release of heat in preparation for physical exertion.