Anxiety disorders are characterized by fear and distress in the absence of objective threat and are accompanied by physiological, cognitive, and affective symptoms. Such fear and distress can occur in both anticipatory forms, as generalized anxiety disorder (GAD), and in acute forms, as in panic disorder. With one-year and lifetime prevalence rates of 18.1% and 28.8%, respectively (Kessler, Chiu, Demler, & Walters, Reference Kessler, Chiu, Demler and Walters2005a; Kessler et al., Reference Kessler, Berglund, Demler, Jin, Merikangas and Walters2005b), anxiety disorders are one of the most common psychiatric conditions.

Given the high prevalence of anxiety disorders, it is important to consider their associated disability. Indeed, anxiety disorders are ranked as the sixth leading cause of disability in both high- and low-income countries (Baxter, Vos, Scott, Ferrari, & Whiteford, Reference Baxter, Vos, Scott, Ferrari and Whiteford2010) and are experienced as equally disabling as many chronic physical conditions (Stein et al., Reference Stein, Roy-Byrne, Craske, Bystritsky, Sullivan, Pyne and Sherbourne2005). Such deficits can include problems with social relationships, responsibilities, and self-care among adults (Hendriks et al., Reference Hendriks, Spijker, Licht, Beekman, Hardeveld, de Graaf and Penninx2014) and diminished academic performance in children and adolescents (Nail et al., Reference Nail, Christofferson, Ginsburg, Drake, Kendall, McCracken and Sakolsky2015). Likewise, anxiety disorders are associated with decreased quality of life (Mendlowicz & Stein, Reference Mendlowicz and Stein2000). Notably, quality of life is also impaired in subthreshold samples (Mendlowicz & Stein, Reference Mendlowicz and Stein2000), suggesting that anxiety-related dysfunction is not limited to those with the most severe disorders. Given such high levels of impairment, it is perhaps unsurprising that anxiety disorders are costly. Anxiety disorders-related disability is associated with an economic burden ranging from $42.3 billion to $46.6 billion annually (Greenberg et al., Reference Greenberg, Sisitsky, Kessler, Finkelstein, Berndt and Fyer1999; Rice & Miller Reference Rice and Miller1998), making anxiety disorders some of the costliest psychiatric conditions (Rice & Miller, Reference Rice and Miller1998).

Despite the high prevalence and associated disability, much remains unknown about the etiology and maintenance of anxiety and related disorders. What is known is that anxiety disorders may be distinguished in part from other forms of psychopathology by the typical age of onset. Indeed, anxiety disorders onset relatively early (median age of onset = 11 years; Kessler et al., Reference Kessler, Berglund, Demler, Jin, Merikangas and Walters2005b) and are highly prevalent among children (Costello, Mustillo, Erkanli, Keeler, & Angold, Reference Costello, Mustillo, Erkanli, Keeler and Angold2003). Although childhood and adolescence appear to represent an important risk window for the development of anxiety symptoms and disorders, researchers continue to struggle to operationalize a comprehensive model that can fully account for this sensitive period.

Research does suggest that treatment for anxiety disorders is often not sought until adulthood (Christiana et al., Reference Christiana, Gilman, Guardino, Mickelson, Morselli, Olfson and Kessler2000), indicating several years of untreated symptoms in many individuals with these disorders. This delay between typical age of onset and treatment may contribute to findings that suggest anxiety disorders are generally chronic (Bruce et al., Reference Bruce, Yonkers, Otto, Eisen, Weisberg, Pagano and Keller2005). Prospective research indicates that the majority of anxiety disorders persist over 12 years, with a lower probability of recovery compared to major depressive disorder (Bruce et al., Reference Bruce, Yonkers, Otto, Eisen, Weisberg, Pagano and Keller2005). Recurrence is also highly likely (Scholten et al., Reference Scholten, Batelaan, Van Balkom, Penninx, Smit and Van Oppen2013), particularly among those with comorbid conditions (Bruce et al., Reference Bruce, Yonkers, Otto, Eisen, Weisberg, Pagano and Keller2005). Further, daily functioning remains diminished in those who remit from an anxiety disorder compared to controls (Iancu et al., Reference Iancu, Batelaan, Zweekhorst, Bunders, Veltman, Penninx and Van Balkom2014). This is notable, given that functional impairment, along with anxiety sensitivity, predicts anxiety disorder recurrence (Scholten et al., Reference Scholten, Batelaan, Van Balkom, Penninx, Smit and Van Oppen2013).

Anxiety disorders are further complicated by high rates of comorbidity, as approximately 90% of those with an anxiety disorder have a history of additional psychopathology (Kaufman & Charney, Reference Kaufman and Charney2000. Indeed, half of those with one anxiety disorder meet criteria for another (Kaufman & Charney, Reference Kaufman and Charney2000). Further, anxiety disorders commonly co-occur with other psychological conditions, including mood disorders, substance use disorders (Kessler et al., Reference Kessler, Chiu, Demler and Walters2005a), and eating disorders (Kaye, Bulik, Thornton, Barbarich, & Masters, Reference Kaye, Bulik, Thornton, Barbarich and Masters2004). Notably, anxiety disorders often precede the development of these disorders (Goodwin & Stein, Reference Goodwin and Stein2013; Rojo-Moreno et al., Reference Rojo-Moreno, Arribas, Plumed, Gimeno, Garcia-Blanco, Vaz-Leal and Livianos2015; Wittchen, Kessler, Pfister, & Lieb, Reference Wittchen, Kessler, Pfister and Lieb2000), suggesting that treating the anxiety disorder may result in improvement in the comorbid condition.

Anxiety disorders also often co-occur with medical conditions. Indeed, anxiety disorders are uniquely associated with medical disorders over and above the effects of mood and substance use disorders (Sareen, Cox, Clara, & Asmundson, Reference Sareen, Cox, Clara and Asmundson2005a), and this pattern of comorbidity is associated with increased illness severity (Katon, Lin, & Kroenke, Reference Katon, Lin and Kroenke2007). Though anxiety disorders co-occur with a wide range of medical conditions, illnesses characterized by pain are particularly common in those with an anxiety disorder (Harter, Conway, & Merikangas, Reference Harter, Conway and Merikangas2003; Sareen et al., Reference Sareen, Cox, Clara and Asmundson2005a). Further, reductions in health-related anxiety are associated with improvements in pain conditions (McCracken, Gross, & Eccleston, Reference McCracken, Gross and Eccleston2002; Spinhoven, Van der Does, Van Dijk, & Van Rood, Reference Spinhoven, Van der Does, Van Dijk and Van Rood2010), suggesting the utility of targeting anxiety comorbid with medical conditions.

Furthering our understanding of anxiety and related disorders can also save lives, as anxiety disorders are linked to suicidal ideation and attempts, even after adjusting for psychiatric comorbidity, in both cross-sectional (Cougle, Keough, Riccardi, & Sachs-Ericsson, Reference Cougle, Keough, Riccardi and Sachs-Ericsson2008; Nepon, Belik, Bolton, & Sareen, Reference Nepon, Belik, Bolton and Sareen2010; Sareen et al., Reference Sareen, Cox, Afifi, de Graaf, Asmundson, ten Have and Stein2005b) and longitudinal samples (Sareen et al., Reference Sareen, Cox, Afifi, de Graaf, Asmundson, ten Have and Stein2005b). Further, one study found that among individuals with a history of suicidality, 70% met criteria for an anxiety disorder (Nepon et al., Reference Nepon, Belik, Bolton and Sareen2010). A similar relationship is also evident among adolescents with anxiety disorders, with increased rates of suicide associated with increased number of anxiety disorders (Boden, Fergusson, & Horwood, Reference Boden, Fergusson and Horwood2007). Although the available literature clearly shows that a preexisting anxiety disorder is an independent risk factor for suicidality and that comorbid anxiety amplifies the risk of suicide attempts among those with mood disorders, the psychobiological processes that may explain this effect remain unclear.

Current understanding of the psychobiological processes associated with anxiety has resulted in significant changes in the diagnostic classification of anxiety disorders in recent years. In the modern classification system, the Diagnostic and Statistical Manual of Mental Disorders (DSM), classes of disorders are clustered around shared phenomenological features, with the defining features of anxiety disorders being symptoms of anxiety and avoidance behavior (APA, 1987). Since the introduction of diagnostic classes in DSM-III (APA, 1980), the anxiety disorders class has consistently included panic disorder with/without agoraphobia, specific phobias, social phobia, GAD, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). However, DSM-5 has represented a notable departure from this standard, such that OCD and PTSD have been removed from the anxiety disorders and placed within two newly created classes, obsessive-compulsive and related disorders and trauma- and stressor-related disorders, respectively (APA, 2013).

These changes have proved controversial. The obsessive-compulsive and related disorders class was introduced on the assertion that OCD is phenomenologically and biologically distinct from anxiety disorders (Stein et al., Reference Stein, Fineberg, Bienvenu, Denys, Lochner, Nestadt and Phillips2010). For example, proponents of the obsessive-compulsive and related disorders class suggest that the distinguishing phenomenon of OCD is not anxiety, but repetitive behaviors and emphasize the unique neural profile of hyperactivity in the fronto-striatal loop in OCD (Stein et al., Reference Stein, Fineberg, Bienvenu, Denys, Lochner, Nestadt and Phillips2010). In contrast, critics of this approach argue that the one of the primary features of OCD is anxiety in response to obsessions and that efforts to adapt classification systems based on findings from neuroimaging research are premature (Abramowitz & Jacoby, Reference Abramowitz and Jacoby2014). Likewise, while proponents of the changes to PTSD in DSM-5 have praised the addition of symptoms to the diagnostic criteria (Kilpatrick, Reference Kilpatrick2013), others have argued that the new criteria result in excessive heterogeneity (Galatzer-Levy & Bryant, Reference Galatzer-Levy and Bryant2013).

Such controversies highlight the limitations inherent to categorical diagnostic approaches. The utility of the diagnostic criteria defined by the DSM is to guide differential diagnosis and selection of treatment and provide a common language for practitioners (APA, 2013). Though the categorical diagnoses contained in the DSM framework arguably imply true distinctions between disorders that represent unique etiologies, DSM-5 notes that such a classification system may not fully account for the various complexities of mental illness (APA, 2013). Indeed, critics of the categorical approach have argued that the excessive rates of comorbidity suggest shared etiology among multiple disorders that the categorical approach would classify as distinct (Widiger & Samuel, Reference Widiger and Samuel2005). For example, high comorbidity between GAD and depression may reflect shared genetic diatheses and overlap of core phenotypic processes, such as negative affect (Mineka, Watson, & Clark, Reference Mineka, Watson and Clark1998).

Likewise, the necessity of “black-and-white” boundaries between disorders in a categorical system has contributed to a proliferation of new disorders designed to bridge the gap between extant disorders, a practice that may reflect artificial cutoffs of dimensional domains (Widiger & Samuel, Reference Widiger and Samuel2005). This practice is seen in the addition of acute stress disorder to DSM-IV to identify pathological stress responses that surpass adjustment disorder but do not meet the minimum duration required for PTSD (Marshall, Spitzer, & Liebowitz, Reference Marshall, Spitzer and Liebowitz1999). In contrast, a dimensional framework is arguably a better representation of complex phenotypes that are unlikely to derive from singular etiologies. In addition to addressing the issues of comorbidity and arbitrary distinctions, a dimensional framework also allows for quantitative descriptions of severity and treatment progress and lends itself to empirical elucidation of physiological underpinnings of observable symptoms (Helzer, Kraemer, & Krueger, Reference Helzer, Kraemer and Krueger2006).

Research has shown that the severity, duration of anxiety, and disability are able to better identify severe chronic course trajectory as compared with DSM-IV categories (Batelaan, Rhebergen, Spinhoven, Van Balkom, & Penninx, Reference Batelaan, Rhebergen, Spinhoven, Van Balkom and Penninx2014). Findings of this sort suggest that a targeted focus on cross-cutting dimensions may explain more variance in anxiety-related processes than diagnostic categories. The purported benefits of such a dimensional approach to psychopathology has led in part to the development of the National Institute of Mental Health (NIH) Research Domain Criteria (RDoC). The RDoC outlines a framework in which five core domains relevant for psychopathology (Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Social Processes, Arousal and Regulatory Systems) can be measured and described at multiple levels ranging from genes to self-report (Insel et al., Reference Insel, Cuthbert, Garvey, Heinssen, Pine, Quinn and Wang2010). RDoC represents a major departure from the categorical diagnoses of the DSM in a push toward defining mental illness by dysfunction along transdiagnostic dimensions. Importantly, in addition to taking a step toward a dimensional diagnostic system, RDoC also asserts that mental illnesses are “brain disorders” that can be understood and measured in terms of dysfunction at genetic and molecular levels (Insel et al., Reference Insel, Cuthbert, Garvey, Heinssen, Pine, Quinn and Wang2010).

The RDoC perspective has been highly debated, particularly among cognitive and behaviorally oriented psychological scientists (Deacon, Reference Deacon2013). The veracity of this perspective remains to be seen, as clinical neuroscience is in its relative infancy. Likewise, the RDoC’s impact on the future of anxiety and related disorders research is unclear. Though neurobiology has been critical for delineating certain mechanisms of anxiety-related pathology, such as fear conditioning (Lissek, Reference Lissek2012), there is concern that behavioral or verbal indices are undervalued in a brain disorders framework. Given that an important goal of the RDoC approach is to inform the development of novel, circuit-based interventions and the personalization of treatments available, it will be vital to examine the extent to which this approach complements existing empirically supported models of anxiety and related disorders.

Treatments of anxiety and related disorders have largely centered on two modalities: psychotropic medications and cognitive behavior therapy (CBT). While a variety of psychotropic medications have been utilized for the treatment of anxiety and related disorders, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the current first-line pharmacological agents due to both efficacy and tolerability (Ravindran & Stein, Reference Ravindran and Stein2010). CBT for anxiety and related disorders generally includes intervention strategies aimed at reducing maladaptive beliefs (e.g., cognitive restructuring) and behavioral avoidance (e.g., exposure) (Hofmann & Smits, Reference Hofmann and Smits2008). Considerable research has found CBT to be efficacious for the treatment of anxiety and related disorders (Hofmann & Smits, Reference Hofmann and Smits2008; Olatunji, Cisler, & Deacon, Reference Olatunji, Cisler and Deacon2010). Extant research comparing CBT to psychotropic medications indicates comparable efficacy, while evidence for an additive effect of combination treatments (i.e., CBT + medication) is mixed (Bandelow, Seidler-Brandler, Becker, Wedekind, & Ruther, Reference Bandelow, Seidler-Brandler, Becker, Wedekind and Ruther2007). However, CBT treatment gains are generally sustained over one to two years (Butler, Chapman, Forman, & Beck, Reference Butler, Chapman, Forman and Beck2006), whereas medication effects are generally lost upon discontinuation (see Otto, Smits, & Reese, Reference Otto, Smits and Reese2005, for a review). Despite the established efficacy of CBT, a substantial proportion of patients do not respond to CBT or relapse, and a paucity of research examines outcomes beyond two years (Arch & Craske, Reference Arch and Craske2009). These findings highlight major areas for improvement to the current “gold standard” of psychotherapy. Paradigm shifts in research, such as the dimensional approach and emphasis on neurobiology espoused by RDoC, may yield novel treatment targets or personalized medicine insights to increase treatment efficacy and decrease nonresponse and relapse.