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ANXIETY DISORDERS 1 [15 CE hours] Anxiety disorders are characterized by states of chronic, excessive dread or fear of everyday situations. The fear and avoidance can be life-impairing and disabling. Anxiety disorders result from the interaction of biopsychosocial factors, whereby genetic vulnerability interacts with situations, stress, or trauma to produce clinically significant syndromes. The influence from hereditary factors and adverse psychosocial experiences on anxiety disorder pathogenesis and pathophysiology is complex, but neuroscience advances have greatly improved the understanding of the underlying factors in the development and maintenance of anxiety disorders. 55 [5 CE hours] It is clear that acknowledgment of the historical context of racism and its current implications is a vital aspect of providing care to a diverse population. Mental health practitioners, medical providers, researchers, community leaders, advocates, activists, and laypersons should work to prevent and effectively treat the psychological and physical distress experienced as a result of the racism faced by African American clients. RACIAL TRAUMA: THE AFRICAN AMERICAN EXPERIENCE
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PSYCHOLOGY CONTINUING EDUCATION
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PSYCHOLOGY CONTINUING EDUCATION
____________________________________________________________________________ Anxiety Disorders PYMA15AD — 15 CE HOURS R elease D ate : 05/01/25 E xpiration D ate : 04/30/28
Anxiety Disorders
11.Discuss the role and efficacy of psychotherapy approaches in the treatment of anxiety disorders. 12.Select a pharmacotherapy option appropriate to a given patient’s specific diagnosis, age, and comorbidities. 13.Devise a strategy for management and follow-up designed to improve outcomes. 14.Provide patient education more effectively, in relation to specific anxiety disorders. 15.Address the efficacy, safety and limitations of novel, emerging, and alternative/complementary approaches to the treatment of anxiety disorders. Faculty Mark Rose, BS, MA, LP , is a licensed psychologist in the State of Minnesota with a private consulting practice and a medical research analyst with a biomedical communications firm. Earlier healthcare technology assessment work led to medical device and pharmaceutical sector experience in new product development involving cancer ablative devices and pain therapeutics. Along with substantial experience in addic- tion research, Mr. Rose has contributed to the authorship of numerous papers on CNS, oncology, and other medical disorders. He is the lead author of papers published in peer- reviewed addiction, psychiatry, and pain medicine journals and has written books on prescription opioids and alcoholism published by the Hazelden Foundation. He also serves as an Expert Advisor and Expert Witness to law firms that represent disability claimants or criminal defendants on cases related to chronic pain, psychiatric/substance use disorders, and acute pharmacologic/toxicologic effects. Mr. Rose is on the Board of Directors of the Minneapolis-based International Institute of Anti-Aging Medicine and is a member of several professional organizations. Faculty Disclosure Contributing faculty, Mark Rose, BS, MA, LP, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned. Division Planners John M. Leonard, MDJohn V. Jurica, MD, MPHMargo A. Halm, RN, PhD, ACNS-BC, FAANRandall L. Allen, PharmD
Audience This course is designed for health and mental health providers involved in the identification, treatment, and care of patients with anxiety disorder. Course Objective The purpose of this course is to provide healthcare profession- als with the knowledge and skills necessary to appropriately identify and treat patients with anxiety disorders, addressing knowledge gaps, enhancing clinical skills, and improving patient outcomes. Learning Objectives Upon completion of this course, you should be able to: 1. Review basic concepts related to anxiety disorders, including safety behaviors/signals and primaryfeatures. 2. Outline the epidemiology of anxiety disorders in the United States. 3. Describe general risk factors for and comorbidities of anxiety disorders. 4. Describe risk factors for and the clinical course of spe- cific anxiety disorders. 5. Discuss the pathogenesis of anxiety disorders in rela- tion to contributing genetic, physiologic, and psycho- logic factors. 6. Review the pathophysiology of specific anxiety dis orders, including social anxiety disorder,agoraphobia, and specific phobia. 7. Apply the clinical and diagnostic criteria for anxiety disorders presented in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 8. Analyze key components of screening and select appropriate screening tools for identification of anxiety disorders. 9. Conduct an informed clinical evaluation and select laboratory testing, in consideration of the differential diagnosis of anxiety disorders. 10.Describe general treatment considerations for anxiety disorders, including predictors of response or nonre- sponse to therapy.
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Anxiety Disorders ____________________________________________________________________________
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____________________________________________________________________________ Anxiety Disorders
Another coping mechanism observed in persons with anxiety disorder is safety signals, defined as the people or objects used to diminish distress in situations that elicit anxiety. Safety sig- nals are also potentially counterproductive; they offer immedi- ate relief but facilitate persistence of the anxiety disorder over time by preventing direct confrontation of feared stimuli in the absence of “safe” objects/people and by maintaining percep- tions of risk/harm and coping inability. A patient’s continued use of safety signals impedes therapeutic progress, in particular the response to exposure therapy. However, safety behaviors may be helpful early in treatment by making exposure therapy more tolerable and less threatening [1]. PRIMARY FEATURES OF ANXIETY AND RELATED DISORDERS The distinguishing features of specific anxiety disorders are summarized in the following section. Related conditions of post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD) are included because, although no longer classed as anxiety disorders by the 2013 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), they are often included in research that pre-dates 2013 and can co-occur with anxiety disorders [2]. Situations or objects that evoke intense anxiety in patients with agoraphobia, social anxiety disorder, or specific phobia are either avoided or endured with significant personal distress. Generalized Anxiety Disorder Generalized anxiety disorder (GAD) is characterized by repeti- tive thinking and intrusive worrying about potentially harmful future events that is persistent (lasting more than a few months) and not restricted to circumstances [3]. While recognizing that some degree of worry may be helpful, patients with GAD report experiencing excessive, uncontrollable worry causing distress or impairment. These patients have physical anxiety symptoms and key psychologic symptoms (i.e., restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and disturbed sleep). GAD is often comorbid with major depression, panic disorder, phobic anxiety disorders, health anxiety, and OCD [3]. Panic Disorder Panic disorder is characterized by recurrent unexpected surges of severe anxiety (“panic attacks”), with varying degrees of anticipatory anxiety between attacks [3]. Panic attacks are characterized by sudden onset of intense fear (terror) accompa- nied by such symptoms as uncontrollable trembling, sweating, palpitations, dizziness, shortness of breath, numbness and tingling, and chest pain. These attacks are often incapacitat- ing, typically peak within 10 minutes and last around 30 to 45 minutes. Most patients also develop a fear of having future panic attacks, which is considered a key element in classifying such episodes as panic disorder [3].
INTRODUCTION Anxiety is an extreme form of worry, life’s adaptative response to perceived impending physical and emotional threats both large and small; as such, anxiety focuses attention and, if necessary, prompts one to prepare for “fight or flight.” Small moments of anxiety are useful and expected in the course everyday life; such experiences are transient, having no sig- nificant impact on social and occupational activities. Anxiety disorders are maladaptive forms of excessive apprehension and fearfulness—taxing, counter-productive, robbing life of its productivity and joy. Anxiety disorders are characterized by several distinct clinical patterns that share a common refrain: acute exacerbation and chronic states of excessive worry and apprehension around otherwise normal circumstance and everyday situations. Anxiety syndromes include fearfulness in response to social and performance expectations, situational and triggered panic attacks, general (anticipatory) anxiety states, and avoidance (safety) behaviors. The diagnosis of anxiety disorder requires that the patient has experienced a certain number of symptoms or symptomatic episodes for more than a minimum specified period, causing significant personal distress and impairing everyday function [3; 350]. Anxiety disorders are thought to develop from the interaction of genetic predisposition in the face of perceived overwhelming challenges to self—biopsychosocial stress or trauma that leads to clinically significant syndromes. The influence of hereditary factors and adverse psychosocial experiences on pathogenesis and pathophysiology is complex, but neuroscience advances have greatly improved the understanding of the underlying fac- tors in the development and maintenance of anxiety disorders.
BACKGROUND
SAFETY BEHAVIORS AND SIGNALS Safety behaviors are coping tactics used by persons with anxiety disorders to prevent, escape from, or diminish the severity of a perceived threat. Safety behaviors are particularly common in persons with panic disorder, agoraphobia, and social anxiety disorder. These behaviors emerge in response to external (e.g., situations, persons, activities) and/or internal (e.g., thoughts, emotions, memories) foci of perceived threat and are either anticipatory (avoidant) or consequential (escape) [1]. While safety behaviors may provide some measure of immediate relief, they have no impact on the individual’s propensity for anxiety, nor do they diminish the frequency and severity of future symptomatic events. However, assessment of safety behavior provides guidance for implementing targeted interventions, and accurate assessment and elimination of safety behaviors is often necessary to maximize treatment of clinical anxiety [351].
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Anxiety Disorders ____________________________________________________________________________
Agoraphobia Around two-thirds of patients with panic disorder develop agoraphobia, defined as fear or avoidance of places or situations from which escape might be difficult or where help might not be available in the event of a panic attack [3]. These places or situations can include crowds, public transportation, or being alone outside of the home [2]. Social Anxiety Disorder Social anxiety disorder (SAD) is characterized by excessive worry and apprehension in anticipation of social interactions and situations, specifically a fear of being negatively evaluated/ judged by others (resulting in embarrassment or humiliation) in social group settings [3]. It is associated with physical and psychologic anxiety symptoms. Specific Phobia Specific, simple, or isolated phobia is excessive and unreason- able fear/avoidance of specific objects or situations such as animals (e.g., snakes, insects); the natural environment (e.g., heights, storms); closed spaces (e.g., elevators, caves); or proce- dures (e.g., venipuncture, dental examination) [3]. Individuals with specific phobia disorder recognize that their specific fear/ avoidance reaction is unreasonable but find it intensely dis- tressing or interfering with everyday life. The most common phobias reported by adults involve animals, heights, and flying. Separation Anxiety Disorder Adult separation anxiety disorder (SEPAD) is characterized by fear or anxiety concerning separation from those to whom an individual is attached. Common features include excessive distress when experiencing or anticipating separation from home and persistent and excessive worries about potential harms to attachment figures or untoward events that might result in separation [3]. Post-Traumatic Stress Disorder PTSD is the persistent fear or episodic severe emotional dis- tress that follows actual or threatened death, serious injury, or psychological shock to the physical integrity of self or oth- ers (the trauma), with ongoing intrusive symptoms related to the traumatic event. Exacerbations are often triggered by recollections, flashbacks, or dreams; manifestations include avoidance symptoms (e.g., efforts to avoid activities or thoughts associated with the trauma), negative alterations in cognition and mood, and hyper-arousal symptoms (e.g., disturbed sleep, hypervigilance, exaggerated startle response) [2]. Obsessive-Compulsive Disorder OCD is characterized by recurrent uncontrollable thoughts and ruminations (obsessions) that lead to restlessness and anxi- ety, followed by impulsive/repetitive physical or mental rituals (compulsions) to alleviate distress. The obsessive-compulsive behaviors are destressing and time-consuming, which impedes normal social and occupational function. Common obses- sions relate to fear of personal contamination, accidents, and
religious or sexual matters; common rituals include washing, checking, cleaning, counting, and touching [3]. Illness Anxiety Disorder Illness anxiety disorder is a somatic-symptom related disorder characterized by excessive or disproportionate preoccupations with having or acquiring a serious illness. This includes exces- sive health-related behaviors and high levels of alarm about personal health status [3]. OVERALL PREVALENCE, RISK FACTORS, AND CLINICAL COURSE Taken together, anxiety disorders (DSM-5 plus PTSD and OCD) have a 12-month prevalence of approximately 19% in the United States, and a lifetime prevalence of approximately 29% [4; 5]. The pattern of sex distribution is consistent among anxiety disorders, and the prevalence of any anxiety disorder is higher for girls/women (23%) than for boys/men (14%) [5; 6]. Anxiety disorder is more prevalent among adolescents 13 to18 years of age (32%) but less severe, with only 8% having experienced severe impairment. The prevalence of anxiety dis- order gradually declines with age, from a high of 23% among all persons 30 to 44 years of age to 9% among those older than 60 years of age. Among surveyed adults having any anxiety disorder, the proportional severity of impairment associated with symptomatic episodes occurring in the previous year was 43% mild, 34% moderate, and 23% serious [5]. PAST YEAR AND LIFETIME PREVALENCE The reported data on anxiety disorders in the United States include 12-month prevalence, lifetime prevalence, and lifetime morbid risk ( Table 1 ). The two lifetime measures differ. Life- time prevalence measures the proportion of the population currently or previously diagnosed with the disorder, while lifetime morbid risk measures the proportion who may develop the disorder at some point, independent of their lifetime history at the time of assessment. By including future cases, lifetime morbid risk is believed to be more accurate. Lifetime prevalence and lifetime morbid risk are usually equivalent for disorders with early-life onset, but diverge for disorders with increasingly later onset. The ratio of lifetime prevalence to lifetime morbidity risk falls below 1.0 in disorders with increasingly later onset; the further the ratio values fall below 1.0, the later the median age of onset [7]. Anxiety disorders with earlier median age of onset are phobias and separation anxiety disorder (15 to 17 years of age), and those with latest age of onset are panic disorder and general- ized anxiety disorder (23 to 30 years of age). Lifetime morbid risk is considerably higher than lifetime prevalence for most anxiety disorders, with magnitude of difference much higher for disorders with later than earlier age of onset. Also, the ratio of 12-month to lifetime prevalence roughly reflects persistence but varies meaningfully in ways consistent with differential persistence of these disorders [7].
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____________________________________________________________________________ Anxiety Disorders
COMPARISON OF PREVALENCE, MORBID RISK, AND RATIO OF LIFETIME PREVALENCE TO MORBID RISK FOR ANXIETY DISORDERS Anxiety Disorder 12-month Lifetime Lifetime Morbid Risk Lifetime/Lifetime Morbid Risk Generalized anxiety disorder 2.0% 4.3% 9.0% 0.5 Panic disorder 2.4% 3.8% 6.8% 0.5 Agoraphobia 1.7% 2.5% 3.7% 0.7 Social anxiety disorder 7.4% 10.7% 13.0% 0.8 Specific phobia 12.1% 15.6% 18.4% 0.8 Separation anxiety disorder 1.2% 6.7% 8.7% 0.8 Source: [7] Table 1
OVERALL RISK FACTORS Demographic
CLINICAL COURSE Anxiety disorders in the aggregate show a U-shaped age of onset—higher in childhood and young adulthood and lower in adolescence. The greatest concentration occurs during transi- tion to early adulthood. Unlike biologically driven pubertal transitions, adulthood transitions involve distinct psychosocial events (e.g., independent living, full-time employment), and this represents a key period for understanding the develop- ment of adult anxiety disorders such as panic disorder and agoraphobia [10]. Community studies of persons with sub-diagnostic anxiety symptoms over time often show episodic symptoms and pro- longed periods of remission, with symptoms reappearing or worsening during adverse life events and psychosocial stressors. In contrast, studies of clinical anxiety disorder populations typically show a chronic course with fluctuating symptom severity between periods of remission and relapse, with long- term course varying by disorder [3]. Healthcare Utilization Distressing anxiety symptoms oftentimes consist of somatic complaints, prompting patients to visit an emergency facility or seek out a primary care provider. If anxiety disorder goes unrecognized or is considered a secondary issue, costly medi- cal testing and delay in effective care may result. Societal costs resulting from misdiagnosis, ineffective treatment and work absenteeism attributable to anxiety disorders are substantial. The direct medical expenditure associated with anxiety in adults, including inpatient visits, prescription costs, and office- based visits is estimated at $33.7 billion annually [354]. Recog- nition of the patient with a pattern of subjective worrying and anxiety, coupled with validated screening, targeted examination and selective testing enhances diagnosis. Effective treatment with pharmacotherapy or cognitive-behavioral therapy (CBT) can be expected to relieve symptoms and minimize costs [2; 3].
The odds for a lifetime diagnosis of any anxiety disorder were calculated, and the same pattern was found for past 12 month diagnosis [8]. These odds are organized according to sex, socioeconomic status, education level, and age. Overall, the risk of developing an anxiety disorder is greater for women/ girls than men/boys. Persons in lower income brackets also incur an increased odds of developing an anxiety disorder compared with those in higher income brackets (48% increased risk with $35,000 to $69,000; 52% with $20,000 to $34,000; 100% with $19,000 or less). Lower educational attainment is also a risk factor. Compared with college graduates, the odds of developing an anxiety disorder are increased 44% with 13 to 15 years of education, 76% with 12 years of education, and 86% with 0 to 11 years of education. These disorders are also 40% more likely in persons 15 to 24 years of age compared with older adults (45 to 54 years of age) [8]. Behavioral Inhibition and Temperament Behavioral inhibition has been defined as a childhood tem- perament characterized by high levels of caution, avoidance, and fearful response to unfamiliar people, objects, and situa- tions [352]. Children who display behavioral inhibition may exhibit limited ability to handle stress as they mature and are at increased risk of developing anxiety disorders later in life. A study of heightened anxiety in young adults during the COVID-19 pandemic found that behavioral inhibition in childhood was linked to worry dysregulation in adolescence, which in turn predicted elevated anxiety during the pandemic when participants had reached young adulthood [352; 353]. Behavioral inhibition and introversion are also strongly linked to later development and severity of situational avoidance, which is a core feature and risk factor in agoraphobia and SAD [9].
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COMORBID DEPRESSION Anxiety symptoms often co-occur with other psychologic symptoms. Depressive symptoms are highly prevalent with more severe anxiety symptoms, with anxiety and depressive symptom severity strongly correlated. Patients with anxiety disorder have high comorbidity rates of major depressive disor- der (almost 50%), schizophrenia, substance use disorders, and physical illness [3; 11]. Overlapping symptoms of anxiety and depression, such as sleep disturbance, fatigue, and difficulty concentrating, make differentiation challenging. Depressive disorders are sometimes termed “anxious-misery” when high levels of sadness and anhedonia are present [2]. Suicidal ideation and rates of suicide attempts are elevated in persons with anxiety disorders, and the suicide risk among patients has been reported as increased by a factor of 10 compared with the general population [54].
female sex, recent adverse life events, and chronic physical (e.g., respiratory and cardiac disorders, dyslipidemia, cognitive impairment) or mental health (e.g., depression, phobia, past GAD) disorders. Other risk factors include poverty, parental loss/separation or low emotional support during childhood, and history of parental mental health problems. Late-onset GAD is described as a multifactorial, stress-related affective disorder resulting from proximal and distal risk factors of which some are potentially modifiable by healthcare intervention [14]. Clinical Course The course of GAD tends to be chronic with fluctuating symp- tom severity, and GAD may “switch” to other diagnoses, par- ticularly depression and somatoform disorders [15; 16]. GAD is associated with impairments in psychosocial functioning, role functioning, work productivity, and health-related quality of life comparable to major depressive disorder or panic disor- der. Patients with GAD and comorbid major depression show significantly greater impairment in health-related quality of life than in either disorder alone. Primary care patients with GAD showed significantly higher annual medical costs than patients without GAD (median $2,375 versus $1,448) and higher mean annual medical costs ($2,138) than patients with other anxiety disorders. GAD is frequently under-recognized in primary care, and only 20% to 32% of patients receive adequate treatment. Suboptimal treatment adds to the health-related quality of life burden of this disorder [17].
SPECIFIC DISORDERS Generalized Anxiety Disorder Epidemiology
Studies show that GAD has a 6.2% lifetime prevalence and a 2.0% to 3.1% past-year prevalence in the U.S. population [350]. The lifetime and past-year prevalences are 3.6% and 2.0% in men/boys and 6.6% and 4.3% in women/girls. Most persons with GAD diagnoses are female. The reported prevalence for GAD in primary care patient panels range 3.7% to 14.8% [54]. Childhood or adolescent onset was found in more than 50% of those seeking help for anxiety, reflecting the chronicity of the disease [2]. Risk Factors No single etiology has been identified for GAD, but it likely involves the interaction of multiple familial/genetic and envi- ronmental risk factors. A review of twin and family studies found significant associations between GAD, other anxiety disorders, and depression, suggesting a common underlying genetic basis. A significant number of patients and their first-degree relatives develop GAD (odds ratio 6:1) [12]. Civil- ian trauma (e.g., motor vehicle accidents, physical or sexual assault, sudden unexpected loss of a loved one, bullying or peer victimization in childhood or adolescence) is a risk factor for GAD [13]. The presence of another anxiety disorder (e.g., panic disorder, SAD, specific phobia) is another possible factor. Panic disorder is comorbid in 25% of patients with GAD [13]. Older adults are the fastest-growing age demographic in the United States. Although late-onset GAD (on or after 65 years of age) is uncommon, clinicians should bear in mind that age-related propensity for anxiety, including the emergence of anxiety disorder, may change over the course of a lifetime. The concerns of aging that may lead to excessive worrying include personal health, the welfare of loved ones, dwindling income, loss of independence, and ability to manage one’s affairs at home. The primary predictors of anxiety in the elderly include
Panic Disorder Epidemiology
In the United States, 4% to 28% of the population experience panic attacks at some time during life. The 2.4% 12-month prevalence of panic disorder in the United States is among the highest worldwide [7; 18]. Panic disorder prevalence in primary care is approximately 7%, and substantially higher in patients presenting with cardiac or gastrointestinal symptoms. Relative to white patients, the odds of developing panic attacks and panic disorder are higher in Native Americans, and lower in Asian, Hispanic, and black patients [18; 19]. Panic attacks are most likely to develop in patients who are in their mid-20s and slightly earlier in men than women. Panic disorder age of onset is usually between late adolescence and 35 years of age, while the age of onset for panic disorder with agoraphobia spans the early 20s to early 30s. Panic dis- order is more common among women, with a 2:1 ratio and increasing to 3:1 with panic disorder with agoraphobia. Panic symptoms during adolescence elevate risks for other anxiety and mood disorders in adulthood. Depressive disorders are highly comorbid (33% to 85%), especially among those with agoraphobia [2; 20]. Panic disorder is highly comorbid with other anxiety, mood, and substance use disorders, including nicotine dependence, and cigarette smoking may increase the risk for later-onset panic disorder [21].
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____________________________________________________________________________ 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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Anxiety Disorders ____________________________________________________________________________
GAD, and nicotine dependence [39]. One study followed 711 participants with anxiety disorder diagnoses over 15 years. At baseline, those with early-onset (≤20 years of age) panic disorder were more likely to have comorbid major depressive disorder, GAD, and SAD. Those with early- onset panic disorder with agoraphobia were less likely to be married and more likely to have comorbid GAD and SAD. Dur- ing follow-up, persons with panic disorder with agoraphobia were significantly more likely to have illness recurrence after periods of recovery, while findings for the other disorders failed to reach significance. This was thought to reflect differences in typical age of onset among anxiety disorders. The onset of panic disorder with or without agoraphobia is usually early adulthood; earlier onsets are relatively uncommon and may signal a particularly pernicious form of illness. The results further support the particularly adverse effects of early-onset psychiatric illness [40].
Brain profiles of children with behavioral inhibition show distinct patterns, including electroencephalography asym- metry, functional differences in amygdala response to facial expression challenge, and structural differences in the ventral prefrontal cortex. Roughly 40% of children with behavioral inhibition eventually develop SAD, and childhood behavioral inhibition is a primary predictor of SAD. Other components of SAD probably appear later in development, including social- evaluative concerns and coping skills deficits that contribute to functional impairment [44; 45]. A bi-directional relationship exists between parenting style and childhood anxiety. Parenting styles of criticism, over-protection, over-control, and lack of warmth can create insecure attach- ment and risk for SAD. Likewise, temperamentally introverted and anxious children may shape and change parenting styles, with parents becoming over-protective or over-controlling [42]. Studies suggest that challenging parenting behavior (especially in fathers) may play a protective role in anxiety development in the most vulnerable children [46; 47]. Early childhood anxiety disorders, especially separation anxiety and other phobias, are associated with elevated SAD risk in adulthood. SAD is highly comorbid with other anxiety disor- ders, mood disorders, and substance use disorders; substance abuse is often used to regulate anxiety symptoms and social skills [48]. Multiple social cues can develop the capacity to elicit anxiety- related symptoms. Learned escape and avoidance behaviors maintain anxiety, interfere with skill development, and can lead to functional impairment and disability over time. Simi- larly, safety behaviors, such as only entering social situations with a trusted companion, averting eye contact, and staying on the periphery of social gatherings, may maintain anxiety-related impairments. Selective attention to social cues of negative evaluation and internal cues supporting danger perception
Social Anxiety Disorder Epidemiology
SAD can develop at any time during a lifespan, but the aver- age age of onset is during late childhood and adolescence. The prevalence of SAD in pre-adolescence is 3.5%, with rates increasing to about 14% during adolescence [41]. The lifetime prevalence of SAD is 13%, and the prevalence in primary care settings (7%) is high compared with that of other anxiety disorders encountered in general practice [19; 350]. Gender distribution is generally equal during pre-adolescence and becomes increasingly more common in girls/women through adolescence and adulthood. An estimated 70% to 80% of individuals with SAD have comorbid anxiety, mood, or substance use disorders. There are cultural variants in Asian and Eastern cultures that involve fears of offending others or making others uncomfortable [2]. Risk Factors A combination of biologic, familial, environmental, and cultural risk factors drive the development of SAD. Life transi- tions, personal loss, poverty, and experiences of humiliation or embarrassment contribute to SAD risk [42]. Compared with data from the general population, first-degree relatives are as much as six times more likely to be at risk of SAD. Concordance rates are 24% in monozygotic twins and 15% in dizygotic twins [43]. Behavioral inhibition, shyness, introversion, and anxiety sen- sitivity are all common among patients with SAD. Emerging early in life, behavioral inhibition is a heritable trait, and 15% to 20% of young children with behavior inhibition exhibit extreme signs. Relative to children without behavioral inhibi- tion, these patients are typically shy, fearful, and cautious and show elevated physiologic arousal signs at rest, such as higher heart rate, increased pupil dilation, and higher cortisol levels.
may develop [49; 50]. Primary Prevention
Childhood presence of fearfulness and behavioral inhibition can lead to chronic, disabling SAD. Early recognition of child- hood impairments and evidence-based treatment intervention may offset the SAD trajectory of persisting into and through adulthood. Educational-behavioral interventions involving older children/adolescents, parents, school staff, and health- care providers have been found to reduce the development of social anxiety [51; 52; 53]. Clinical Course SAD tends to run a chronic course of long duration, associated with substantial impairment of work productivity, and has a reported recovery rate of only 38% [54].
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____________________________________________________________________________ Anxiety Disorders
Specific Phobia Epidemiology
were diagnosed with SEPAD. Patients with panic disorder and SEPAD (versus no SEPAD) were more commonly female and younger and showed higher rates of childhood SEPAD and greater lifetime prevalence of mood disorder spectrum symptoms [63]. Risk Factors Children of adults with anxiety disorders have higher rates of anxiety disorders. Early, traumatic separation from attachment figures and a positive family history of anxiety or depressive disorders may also elevate risk of SEPAD, school phobia, and depressive-spectrum disorders during adolescence or adult- hood. Early, traumatic separation can include prolonged sever- ance of contact with the primary caregiver during the neonatal period; later sudden hospitalization; early loss of attachments from death or divorce; or an interactive pattern with an over- protective, needy, or depressed parent [64]. Clinical Course In one study, children with SEPAD were 3.5 times more likely to later develop panic disorder and more than twice as likely to develop any anxiety disorder but did not significantly differ in later development of depression or substance use disorder. These findings were considered supportive of a developmental psychopathology model of anxiety disorders [65].
Women are two to three times more likely than men to develop phobias, with the exception of blood-injection-injury phobia, which is evenly distributed by sex. Roughly 70% of individuals with specific phobia report more than one clinically relevant fear. Animals and heights are the most common stimuli, fol- lowed by flying, enclosed spaces, and blood-injection-injury. The average period of onset is 7 to 10 years of age, with declining probabilities of onset into later adulthood. Most animal phobias develop before 8 years of age [2; 41; 56]. The average age of treatment engagement is 31 years, although only 8% of persons with specific phobia are reported to seek treatment [56]. The odds of developing phobias are significantly less in His- panic and Asian individuals and greater in white individuals. Animal fears are prevalent in Japan and Hong Kong [56; 57]. Risk Factors For specific phobias, familial concordance rates among first- degree relatives are moderate. The greatest heritability indices are found in animal and blood-injection-injury phobias [58; 59; 60]. Intense anxiety or unexpected panic responses in the presence of specific objects or situations can mark phobia onset but are not the sole causal route. Disgust, either alone or combined with fear, may trigger the onset and maintenance of animal (particularly spiders, snakes, and worms) or blood-injection- injury phobias. Onset can occur indirectly by observing oth- ers reacting fearfully. Some stimuli are more likely to induce phobias than others (e.g., animals vs. electrical outlets) through evolutionary threat relevance. Phobia onset can be precipitated by relationship problems, relo- cation, employment loss, or economic difficulties. In addition, anxiety, mood, or substance use disorders can co-occur with or predate phobia onset. Substance use disorder can maintain phobic symptoms. Phobia symptoms in adolescence predict adult symptoms but are not a risk factor for developing other anxiety, mood, or substance use disorders.
ETIOLOGY AND PATHOPHYSIOLOGY
ANXIETY DISORDERS IN GENERAL Anxiety disorders are characterized by diverse neuroendocrine, neurotransmitter, and neuroanatomical disruptions, the result of interactions between multiple genetic, environmental, and social factors. Although each disorder may have unique features, this group shares some underlying pathophysiology. Pathologic Alterations in Brain Structure and Function Fear and anxiety are thought to involve two major brain cir- cuits: the limbic system and the prefrontal cortex. In the limbic system, which consists of the amygdala, hippocampus, central nucleus of the amygdala, insular cortex, and cingulate cortex, emotion-processing brain structures generate primitive innate responses to simple, overtly threatening stimuli. Functions of limbic structures include processing emotionally important external stimuli and initiating behavioral responses; mediating expressions of fear, aggression, and defensive behavior; and forming and retrieving emotional and fear-related memories [66; 67]. The prefrontal cortex, comprised of the orbitofrontal cortex and the prefrontal, ventromedial, and dorsomedial prefrontal cortex, dampens emotional responses to anxiety- inducing stimuli. The prefrontal cortex functions to regulate impulses, emotions, and behavior via inhibitory “top-down” control of emotional-processing structures; this works to con- trol impulses and regulate mood [66; 67].
Adult Separation Anxiety Disorder Epidemiology
The lifetime prevalence of adult SEPAD is 6.6% in the general population, 12% to 40% in psychiatric clinic settings, and more than 75% among those seeking treatment at anxiety disorder clinics [61]. In adults with lifetime SEPAD, 22.5% have childhood age of onset that persisted into adulthood, while 77.5% had adult onset. Girls/women show higher overall prevalence than boys/men and substantially higher rates of childhood-onset SEPAD persisting into adulthood [62]. SEPAD and panic disorder are highly comorbid in clini- cal settings. Among adult patients with panic disorder, 53.2%
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