____________________________________________________________________________ Anxiety Disorders
Risk Factors As with GAD, the etiology of panic disorder probably results from a combination of risk factors. There is a five-fold greater risk of developing panic disorder when the disorder is pres- ent in first-degree relatives. Shared genetic factors account for 30% to 40% of panic disorder heritability [12]. In addition, major adverse life events, especially those involving physical threat (e.g., physical abuse, sexual assault, military service in a combat zone), precede the onset of panic attacks in roughly 80% of patients. Trauma history is prevalent in patients with panic disorder, especially women [22]. Behavioral inhibition may contribute to panic risk in adult- hood. Learned escape and avoidance behaviors can maintain the condition and worsen functional impairment over time. Anxiety sensitivity, or the tendency to catastrophically mis- interpret physical symptoms as dangerous, is a risk factor for panic disorder. Personality pathology, particularly avoidant and dependent personality traits, are predictors of panic disorder or agoraphobia development [23; 24]. Asthma severity is associated with an incremental risk for panic disorder, and respiratory variability may also increase risk for later onset panic disorder [25]. Baseline respiratory abnormalities are specific to panic disorder pathophysiology [6]. As noted, cigarette smoking and nicotine dependence is disproportionately high among patients with panic disorder and may be temporally related to elevated risk for developing panic disorder [26]. Additionally, panic attacks may be related to poorer cessation outcome during smoking treatment among patients with cancer [27]. Caffeine use is also positively cor- related with increased anxiety symptoms and risk of inducing panic attacks in patients with panic disorder [28]. Clinical Course Prospective studies of panic disorder show high rates of symptom chronicity, relapse after remission, and “switching” to other diagnoses [29; 30]. Panic disorder symptoms remain persistent for 50% to 80% of cases even after treatment, increasing disability and impaired quality of life [31].
Risk Factors Much of the published agoraphobia research assumes panic disorder causation or comorbidity. As such, many of the known risk factors are the same. Comorbid panic disorder and agora- phobia aggregate in families, while agoraphobia without panic disorder is non-familial but may enhance familial transmission of panic disorder [33]. The risk of agoraphobia development in patients with panic disorder is elevated with female sex, more severe dizziness during panic attacks, cognitive factors, dependent personality traits, and SAD. Panic disorder with agoraphobia is associated with greater severity and worse prognosis [34]. Longitudinal studies show low remission rates (0% to 23%) over time in panic disorder or agoraphobia, and subjects with panic disorder with agoraphobia or agoraphobia with panic attacks at baseline were more likely to develop agoraphobia, panic attacks, and other anxiety disorders and experience greater severity (e.g., impairment, disability, treatment-seeking, comorbidity) than subjects with panic disorder without agora- phobia or agoraphobia without panic attacks at baseline [35]. A late-life subtype of agoraphobia (onset at or after 65 years of age) was identified through assessing elderly patients at baseline and four years later. Baseline agoraphobia prevalence was 10.4%, and 11.2% developed agoraphobia during the four-year follow-up. Agoraphobia in the elderly, unlike younger populations, was not more common in women and not associ- ated with panic attacks. Risk factors for late-onset agoraphobia include severe depression, trait anxiety, and poor visuo-spatial memory [36]. Incident anxiety also appears to develop in response to subjective memory complaints independent of depressive symptoms [37]. Patients with panic disorder who experience their first panic attack while driving or using public transportation had higher rates of comorbid agoraphobia. Those with first panic attack at home had higher fear-of-dying rates than with first panic attack outside of the home and felt more severe distress from their first panic attack independent of whether agoraphobia developed. Treatment of patients with panic disorder whose first panic attack was at home should address secondary aspects of fear and distress elicited by the attack [38]. Clinical Course In persons with panic disorder with or without agoraphobia, the strongest predictors of incidence and relapse were history of panic attacks, GAD/major depression, nicotine dependence, female sex, younger age, and major financial crises. Most pre- dictor variables were similar between panic disorder and panic disorder with agoraphobia. Clinicians should bear in mind the characteristic relapsing-remitting nature of panic disorder/ panic disorder with agoraphobia in order to avoid prematurely reducing or eliminating effective treatments. Close attention should be paid to concurrent factors linked to relapse that can be clinically addressed, such as comorbid major depression,
Agoraphobia Epidemiology
Agoraphobia usually, but not always, occurs with panic dis- order. In community populations, about 25% of those with panic disorder also have agoraphobia, but the proportion is substantially higher in clinical populations [20]. Agoraphobia was made an independent diagnostic entity in the DSM-5, and accordingly, epidemiologic and clinical data that consider agoraphobia in the absence of panic disorder are pending. In the DSM-IV-TR, panic disorder could be specified with or without agoraphobia. Lifetime and 12-month prevalence of panic disorder with agoraphobia were 1.0% and 0.5%, respectively [32].
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