Environmental Factors in the Etiology of Anxiety1

Karrie J. Craig, Kelly J. Brown, and Andrew Baum

Anxiety is a common human emotional state, and anxiety disorders represent a major class of clinical problems that occur throughout the lifespan. The construct has become intertwined with concepts such as stress and uncertainty, and anxiety disorders have been extended to include syndromes that do not feature anxiety as a primary presenting symptom. Regardless, anxiety remains a central concept in psychopharmacology. This chapter considers the etiology and maintenance of anxiety, with emphasis on exogenous factors such as stress. Research on environmental influences in the development of anxiety and anxiety disorders is described and major models of anxiety, emphasizing exogenous factors in the etiology and maintenance of these affective states, are considered. Distinctions between anxiety and fear and among the different anxiety disorders, as well as an evaluation of research linking these two constructs, provide a useful perspective on the origins of anxiety.

Anxiety is a complicated concept, in part because it represents different things in different contexts. Most think of it either as a mood state or a mood disorder, some view it as a proxy for stress, and still others discuss its cognitive aspects with little reference to mood. As a mood state or feeling state, anxiety usually refers to the experience of fear, apprehensiveness, nervousness, panic, restlessness, tension, and agitation (69). Manifest symptoms include trembling, fainting, headaches, and sweating, possibly elevated blood pressure, and changes in other psychophysiological indices such as heart rate, muscle tone, and skin conductance. Anxiety disorders are also associated with these physical and emotional symptoms, but are several magnitudes more severe, debilitating, and/or intrusive. The defining features of anxiety disorders in DSM III-R are symptoms of anxiety and avoidance behavior (2). Hyperarousal is also a frequent symptom of these syndromes. Representative of these disorders are (a) panic disorder and generalized anxiety disorder, in which anxiety is usually the primary symptom, and (b) phobic disorders, in which anxiety is experienced as if one is confronted by the feared stimulus and avoidance is very common.

Researchers have adopted a range of outcomes used to measure anxiety. Self-report of mental state, mood, behavior, and symptom experience has been used extensively, as in the State-Trait Anxiety Inventory (65). Other scales also measure anxious symptoms, and consensus has identified primary and secondary symptoms of anxiety: nervousness and fear, fears of fainting and losing control, and avoidance (69). Adequate understanding and study of anxiety requires additional attention to several complicating factors.

One of the primary reasons for confusion about anxiety is its similarity to fear. Both of these mood states involve some sense of dread or apprehensiveness, and fear may be experienced as "part" of anxiety. Because they share a number of characteristics, it is often difficult to distinguish between them; some researchers have suggested that they are indistinguishable (53). Others believe that fear and anxiety are clearly distinct and separate phenomena (4).

Initial distinctions between anxiety and fear appear to have arisen accidently by early translations of Freud, mistaking "Angst," the German word for fear, to mean anxiety (35, p. 389). Freud did not make the distinctions between fear and anxiety that are made by some modern psychotherapists—namely, that anxiety is associated with a repressed unconscious object and fear is linked with a known external stimulus. In other words, an approaching storm would cause fear, and unresolved conflict might cause anxiety. Although intuitively attractive, this distinction does not always hold because fear may be manifested by the displacement of a repressed internal thought to an external object. In addition, a specific external threat can cause anxiety and fear as correlates of the primary threat.

Other distinctions between fear and anxiety focus on (a) the presence or absence of a "consensually determined" threat, (b) the degree to which responses to the threat are in line with its dangerousness, and (c) the potential adaptive value of these responses (4). In these instances, fear refers to realistic or adaptive responses, whereas anxiety refers to less realistic or more inappropriate reactions. Distinctions based on these features are based on self-report of similar phenomena, making them less useful and sometimes arbitrary. However, they provide some additional context for defining anxiety in spite of the difficulty inherent in operationalizing the constructs.

Both fear and anxiety function as alerting signals to warn of danger. Fear involves sympathetic arousal, readying the body and preparing it for action against immediate danger. Miller (45) described two general responses to fear: (i) the excitatory fight or flight response initially postulated by Cannon (14) and (ii) an inhibitory, presumably parasympathetic-based response. As sympathetic arousal, the fight or flight response includes increased heart rate, increased cardiac output, antidiuresis, dilation of skeletal blood muscles, constriction of gut blood vessels, and a surge of catecholamine release. This excitatory reaction can be contrasted with the inhibitory pattern, involving tonic immobility and freezing or feigning death in extreme cases (45). This behavior appears to help conceal or protect the body from harm. The physiological correlates of this inhibitory response include inhibition of skeletal movement, increased peripheral resistance, and little or no change in diuresis or heart rate. The nature of the stimulus, intensity of the fear, previous experience, and genetic factors appear to influence these general patterns and determine which will be elicited.

Anxiety is also composed of two components. Unlike fear, however, the responses are temporally linked such that one follows the other. The first response to anxiety is the initiation of physiological arousal and recognition of impending danger (35). Coincident with the elicitation of sympathetic arousal, as this arousal and activity are unfolding, one becomes aware of a range of bodily changes. This second aspect of anxiety is primarily cognitive, serves to differentiate anxiety from fear, and may influence the extent to which one suffers from anxiety disorders.

Because anxiety and fear are among the body's first defenses against harm, they may share redundant mechanisms; in general, psychometric and physiological data suggest that they share considerable overlap. Based on a review of studies that manipulated anxiety and fear through brain lesions, electrical stimulation, and pharmacological manipulations, it appears that both fear and anxiety operate through activation of the noradrenergic pathway originating in the locus coeruleus (30). In contrast to fear, which triggers the fight or flight response through this mechanism, anxiety appears to activate the noradrenergic system in conjunction with serotonergic pathways originating in the raphe nuclei (30). The result is a priming of the fight or flight response, which is simultaneously suppressed through serotonergic inhibitory pathways.

Different etiologies, response patterns, time courses, and intensities of anxiety and fear make distinctions between them justifiable. Although both anxiety and fear are alerting signals, they appear to prepare the body for different actions. Anxiety implies that danger may be near and that the fight or flight response may be necessary—hence the priming effect described by Gray (30). Anxiety is a generalized response to an unknown threat or internal conflict, whereas fear is focused on known or unknown external danger. Anxiety is usually long-lived (there is no obvious stimulus to escape or avoid), but fear is usually event-limited. Where fear represents response to finite potential harm that can be avoided if something is done, anxiety is characterized by less well-defined threats that are not readily addressed. Fear also differs from anxiety in that it is usually unanticipated, is dependent upon the termination of the feared object, is often very intense, and occurs in self-limiting single episodes.

Both anxiety and fear are usually experienced well within the range of normal emotional experience. To some extent, anxiety is a routine emotional state experienced as part of everyday life. The ability to anticipate and prepare is associated with the ability to experience fear and anxiety as we continually strive to adapt to a changing world. When anxiety becomes abnormally intense and/or prolonged, it ceases to play a role in this continual adaptation. Pathological anxiety occurs when normal daily functioning is disrupted by inappropriate responses to internal conflicts or anticipation of some unknown threat. These exaggerated responses can be qualified in terms of duration or intensity. Characteristics of pathological anxiety can include repressed thoughts, negative conditioned responses, counterproductive thought patterns, poor coping strategies, and increased sympathetic tone of the autonomic system (35).

Pathological anxiety is reflected in symptoms of organic anxiety syndrome, adjustment disorder with anxious mood, or an anxiety disorder. The DSM-III R (2) lists six separate categories of anxiety disorders: generalized anxiety, panic disorders, obsessive–compulsive disorder, post-traumatic stress disorder, and phobias (e.g., simple, social, and agoraphobia). Disorders that characteristically involve prominent anxiety or phobic avoidance but do not meet the diagnostic criteria for a particular anxiety or adjustment disorder with anxious mood are classified as anxiety disorders not otherwise specified (NOS). The DSM-III R (2) also includes a subclass of anxiety disorders found in children and adolescents, including separation anxiety, avoidant disorder, and overanxious disorder. Although the anxiety disorders are grouped together because the fundamental symptom in all these syndromes is thought to be anxiety, these disorders represent a heterogeneous group of dysfunctional states, each with its own etiology and responses to treatment (35).

This syndrome is characterized by unrealistic and excessive apprehension about unspecified future events. It has been classified as a chronic disorder lasting longer than 6 months and encompassing at least two or more life circumstances (2). Specific symptoms include motor tension (e.g., trembling, twitching, restlessness), autonomic hyperactivity (e.g., shortness of breath, tachycardia, sweating, nausea, abdominal distress), vigilance, and scanning (e.g., exaggerated startle, difficulty concentrating, irritability). At least six of these symptoms must be persistent and bothersome and not just experienced during an acute episode.

Panic disorders are defined as conditions in which anxiety manifests itself as recurrent panic attacks characterized by discrete periods of intense fear and discomfort (2). They typically begin with the sudden onset of extreme apprehension or terror and are often accompanied by feelings of impending doom. The attacks are unpredictable and do not occur immediately before or during exposure to specific situations. However, some circumstances can increase the likelihood of an attack at some time during exposure. In these situations, panic attacks can lead to the avoidance of specific events, and the disorder is said to be accompanied by agoraphobia.

Panic attacks are accompanied by a shortness of breath, the sensation of smothering, dizziness, faintness, tachycardia, shaking, abdominal distress, depersonalization, numbness or tingling, chills, chest pains, and a fear of dying or going crazy. During an attack, some of these symptoms develop suddenly and increase in intensity within 10 min of the beginning of the first noticed symptom (2). To be diagnosed as having a panic disorder, four such attacks must occur within a 4-week period or one or more attacks must have been followed by a prolonged period of persistent fear of having another.

The essential features of obsessive–compulsive disorder are recurrent obsessions or compulsions that are strong or persistent enough to cause distress (2). Obsessions are defined as persistent ideas, thoughts, or images about some object or action. Attempts to ignore or suppress these intrusive and often senseless obsessions with other thoughts or actions are usually time-consuming and can interfere with normal daily functioning. Compulsions are repetitive, purposeful, and intentional behaviors that may accompany obsessive thoughts. These behaviors are performed in a stereotypic manner, are ordinarily excessive, and usually follow rules that are not clearly tied to the thoughts or ideas they are trying to neutralize. These acts are initially performed as a function of a conflict between wanting to perform the behavior and wanting to resist it. This conflict may end with repeated failure and mounting tension. The person may recognize that the behavior is unreasonable and may find it unpleasurable, but compulsive behaviors typically provide a release of tension.

Unlike most of the anxiety disorders, PTSD does not feature anxiety as a primary presenting symptom. It typically follows a psychologically distressing event that is outside the realm of normal human experience, events that often involve a threat to life (2). These events may be experienced alone (as in assault or rape) or in groups (e.g., combat, disasters) and include natural and accidental or deliberate human-made emergencies. Symptoms characteristic of PTSD are often intensified or precipitated when cues or reminders of the event are present. The disorder is characterized by victims' reexperiencing the traumatic event in a variety of ways. The event can be relived through recurrent, intrusive thoughts, vivid and distressing dreams, and flashbacks accompanied by intense feelings of reliving the trauma in a dissociative state. Cues or symbols that resemble the event can cause intense psychological distress and are persistently avoided in controllable thoughts and actions.

"Psychic numbing" is another common symptom of PTSD and is characterized by diminished responsiveness to everyday events, feelings of detachment and estrangement to loved ones, loss of interest in previously enjoyed activities, and difficulty in experiencing emotions. In addition, PTSD victims have a persistent elevated level of arousal, manifested in sleep problems, irritability, difficulty concentrating, hypervigilance, an exaggerated startle response, aggression, and increased sympathetic arousal and reactivity. Diagnostic criteria require that all categories of symptoms (reexperiences, emotional numbness, and increased arousal) be met during the same period of at least a month. A delayed-onset diagnosis is applied if the symptoms appear more than 6 months after the event has passed (2).

The DSM-III R (2) divides phobias into three specific types: agoraphobia, social phobias, and simple phobias. Agoraphobia is a fear of being in places or situations from which escape may not be immediately available (fear may be generated by the desire to avoid embarrassment if a limited symptom attack should occur). Symptoms often include dizziness, depersonalization, falling, loss of bladder or bowel control, vomiting, and cardiac distress. These symptoms need not have been experienced before.

Social phobias are reflected in the persistent fear that one or more situations may expose a person to unusual or unacceptable scrutiny by others, causing the person to act inappropriately. Exposure to these stimuli usually leads to immediate symptoms of anxiety, including panic, tachycardia, sweating, and breathing difficulty. Anticipation of encountering a social situation usually leads to avoidance, and this often interferes with normal functioning. The afflicted individual recognizes that the fear is excessive and unreasonable; this may, in turn, increase distress associated with the situation.

Simple phobias are characterized by persistent fear of a circumscribed object or situation other than having a panic attack or being socially embarrassed. Sometimes referred to as specific phobias, these disorders are initiated by exposure to the stimulus which invariably evokes an immediate anxiety response which will predictably increase or decrease in intensity as the location or nature of the stimulus changes. Anticipatory anxiety is common and these stimuli are avoided, which can lead to a disruption in daily living. As with other phobias, individuals are normally aware of the extent of experienced fear and this adds to the anxiety evoked by the stimulus.

Anxiety disorders found in children include separation anxiety disorder, avoidant disorder, and overanxious disorder (2). In separation anxiety and avoidant disorder, anxiety is focused on a specific situation. Overanxious disorder is generalized to a variety of situations. Separation anxiety manifests itself as excessive anxiety over separation from someone to whom the child is attached. The reaction can be so strong that the victim experiences panic. The child may display clinging behavior and be unable to stay alone in a room for fear that something will happen to the person they are attached to or to them.

Children may also fear animals, monsters, and situations that are perceived as a threat to the integrity of the family. Some children may experience anticipatory anxiety when separation is imminent, and this anticipation is commonly accompanied by physical complaints such as gastric distress, headaches, nausea, and vomiting. Behavioral problems such as trouble sleeping alone, recurrent nightmares, social withdrawal, apathy, sadness, temper tantrums, difficulty concentrating, and aggressive behavior can occur during times of separation. Similarly, avoidant disorders are characterized by the excessive avoidance of contact with unfamiliar people and a desire for involvement with family members and friends who the child finds warm and satisfying. Social functioning with peers is hampered and the child appears socially withdrawn, embarrassed, and timid when around strangers.

Unlike separation and avoidant disorders, overanxious disorder is a generalized excessive or unrealistic anxiety or worry. A child with this disorder has the tendency to be self-conscious and worried about future events and past behaviors. The disorder is accompanied by feelings of inadequacies, constantly being judged by authority figures or peers and an excessive need of reassurance. Somatic symptoms such as gastrointestinal distress, headaches, a lump in the throat, shortness of breath, and nausea are manifest in some cases. Difficulties sleeping are also common. In general, the child appears nervous and tense, and symptoms persist for at least 6 months.

A number of human models of anxiety have been proposed, and several are linked to different approaches to nonpharmacologic treatment of anxiety disorders. In this section, two major developments in the evolution of these models are described. Animal models of anxiety are also of considerable interest to those interested in the biological bases of anxiety and in psychopharmacologic treatments for anxiety disorders. Because of the ethical problems inherent in studying extreme or disturbing human emotions, animals are frequently used to study conditions or emotions such as fear, phobias, and anxiety. Comparisons are usually made between a proposed animal model and the human disorder in terms of underlying mechanisms, treatment responsiveness, and etiology. There is no single comprehensive animal model of anxiety, but there are a number of models that meet specific criteria necessary for meaningful comparisons to at least one aspect of the human experience. Models discussed in this section will include the subset of animal models designed to study environmental factors that contribute to the development of anxiety or anxiety disorders.

Animal models used to test etiologic theories of anxiety are typically designed to produce fear and "anxious behaviors." Both can be adaptive if they inhibit potentially harmful behaviors or, conversely, cause the animal to act in such a way to allow it to escape an aversive situation. As noted earlier, anxiety and fear are not readily separable behaviorally or physiologically, but are differentiated by their distinct etiology. Causes of anxiety are usually associated with nonspecific events or stimuli such as being in a novel environment. Consequently, anxiety is usually defined as a generalized, unfocused response. Fear normally results from an experienced or known danger in the immediate environment. A rat that has been shocked in a particular setting might vocalize or try to escape when placed in the same setting. Thus, fear is usually used to describe a focused response to a known object or experience.

Animal models of anxiety and fear are often based on the assumption that the cause of the emotional response in the animal would be sufficient to cause a similar emotional response in a human. Situations involving the unknown, reminders of negative experiences, conflict, unpredictability, and uncontrollability are commonly used as anxiety-evoking agents in both human and animal studies. Using animals to approximate human conditions involves operationalizing these environmental factors in order to evaluate potential anxiety-inducing effects. The goal is to develop models that closely parallel theories based on clinical observations, including the conditioned emotional response, fear-potentiated startle, punishment–conflict, and separation and abandonment models of anxiety.

Conditioned emotional responses are readily produced in animals through a series of pairings and nonpairings of an unconditioned stimulus (US) (such as shock) with a conditioned stimulus (CS) (such as a tone). The US–CS contingency is important in determining whether emotional conditioning is developed, inhibited, or retarded (54). In time, shock-tone pairings come to elicit a conditioned emotional response that is characterized by a decrease in baseline behavior, usually measured in number of lever responses. This specific phenomenon is referred to as conditioned emotional response (CER). Conversely, when a shock and a tone are explicitly not paired, the tone represents a period of safety and becomes a conditioned inhibitor of fear or anxiety (59). The result is a suppression of lever pressing only in the absence of the tone.

The situations that are produced by this conditioning procedure are thought to closely approximate the human fear experience, but they are not readily generalizable to feelings of anxiety. In the CER paradigm the unpleasant affect or absence thereof is predictable and expected. In contrast, anxiety is often triggered by uncertainty and anticipation of unknown events. This type of environment is produced in animal models by designing conditions where the tone and shock are neither paired nor unpaired (58). In this situation, the tone provides no information about the likelihood or actual occurrence of the impending negative event, producing a general state of suppressed activity at all times. Unpredictable and uncontrollable shocks or experiences in environments appear to produce a negative emotional state and leave animals susceptible to the development of ulcers and unrestricted tumor growth (e.g., see ref. 71).

The acoustic startle reflex in the rat can be exaggerated by presenting an eliciting auditory startle stimulus in the presence of a conditioned stimulus that has previously been paired with shock (12). This is referred to as the fear-potentiated startle paradigm, in which fear or anxiety is operationally defined as an elevated startle response. Under normal conditions, the acoustic startle response occurs naturally in mammals as a defensive reaction to external auditory stimulation, characterized by a series of rapid movements beginning at the head and moving towards the tail, causing the contraction and extension of major muscle groups (19). In the fear-potentiated startle paradigm the conditioned stimulus itself does not elicit a response and the startle-eliciting stimulus is never paired with shock. Fear-potentiated startle is said to occur only when the startle-eliciting stimulus creates a greater response in the presence of the conditioned stimulus compared to when it is presented alone (19).

Potentiated startle only occurs following paired presentations of the conditioned stimulus and the stressor. Unlike other animal models of fear and anxiety that use the suppression of ongoing behaviors as an indicator of an emotional state, the potentiated startle paradigm equates enhanced response output with the desired affect (19). Because emotionality in the potentiated startle paradigm is manifested as increased responding, it provides a distinct measurable symptom of anxiety separate from other animal models of affective disorders characterized by behavioral inhibition such as depression or learned helplessness. In addition, the fear-potentiated startle response provides a parallel to increased arousal seen in humans in many cases of PTSD. Symptoms of PTSD include elevated sympathetic arousal and an exaggerated startle response (2). Furthermore, drugs such as yohimbine, which induce anxiety in normal people and enhance it in anxious people, increase the potentiated startle reflex in rats (19). Drugs that reduce anxiety in people also decrease the fear-potentiated startle response in rats (43). Again, these drug effects are of particular value because they cannot be attributed to a decrease in general performance as with animal models that measure anxiety through marked changes in making or withholding required learned responses.

In general, punishment–conflict tasks involve the use of operant techniques to elicit well-established behaviors and then use aversive stimuli to suppress them by punishing the behaviors when they occur. This suppression of responding is thought to mimic the passive–avoidant component of anxiety, manifested in many animals and humans in anxious or fearful situations. It is characterized by the expending of energy to extinguish specific behaviors to avoid contact with feared objects and situations.

The development of this model of anxiety was initially based on Estes and Skinner's (21) discovery that a conditioned stimulus such as shock will suppress the performance of appetitive instrumental responding. In contrast to conditioned emotional response paradigms, punishment procedures do not use explicit conditioned stimuli to signal the impending aversive unconditioned stimuli. Instead the environment provides the necessary cues that signal that repeated exposure is paired with punishment. These environmental cues come to elicit conditioned emotional responses which are incompatible with the punished behavior. Animals are left in a state of conflict by having to balance the positive features of the reward (i.e., food, water) against the negative aspects of receiving shock (26). The punished behavior is eventually suppressed, presumably by inhibiting motivation to respond to the positive reinforcement (50).

Suppressed behavior is based on the predictability and objectivity of the presentation of an aversive stimulus, and the resulting conditioned responses are quite different from generalized anxiety, which is often unpredictable and uncontrollable and often involves some aspect of uncertainty. Although these variables are manipulated in animal models of depression, they have generally been overlooked in models of anxiety. Animal models of depression assume that uncontrollability leads to escape and avoidance deficits, whereas anxiety models characterize anxiety as the use of excessive avoidant behaviors. This discrepancy is somewhat resolved by distinguishing between active and passive avoidance. It is suggested that while uncontrollability may lead to impaired active avoidance, it can facilitate the use of passive avoidance (55).

Animal models have shown that uncontrollable and/or unpredictable aversive events produce a wide range of emotional disturbances in animals, compared to controllable and predictable events of the same duration and intensity. These emotions include intense and persistent fear and physiological arousal (46, 47). It has been suggested that these models produce generalized fear and arousal accompanied by discrete fear, analgesia, and avoidant behaviors and may parallel the symptom cluster of post-traumatic stress disorder consisting of hyperarousal, reexperiencing, numbing, and avoidance (24).

Animal models of anxiety also have been based on the manipulation of social interactions. One such model involves the separation of an animal from an object of attachment. Rhesus monkeys that have been forcibly separated from an attached object during rearing have been shown to exhibit fear behaviors in the absence of any immediate danger (67). During maternal or peer separation, nonhuman infant primates become hyperactive and show a marked increase in adrenal–pituitary activity (10). Behaviors following this initial reactive stage have been linked to a panic attack. Like anxiety, the intensity and frequency with which these behaviors are induced are dependent upon the type and amount of stress encountered (67).

One of the major developments in the study of human anxiety was the distinction between state and trait anxiety. Initially differentiated by Cattell and Scheier (15) in 1958, state and trait anxiety have been used to indicate different constructs. Spielberger (65) has proposed a conceptual definition of state anxiety (S-anxiety), suggesting that it consists of subjective, consciously perceived feelings of tension, apprehension, nervousness, and worry, accompanied by or associated with activation and arousal of the autonomic nervous system. It has become essential in the study of anxiety and stress to differentiate between (a) S-anxiety as a transitory emotional state and (b) relatively stable individual differences in anxiety as a personality or dispositional trait (T-anxiety).

There are several paper and pencil instruments that can be used to measure fluctuations in S-anxiety as various events (stressors) occur. These self-report scales include the Affect Adjective Check List (75) and the S-anxiety scale of the State-Trait Anxiety Inventory [STAI (65)]. The STAI has been used to measure anxiety in thousands of studies since it was published in 1970, using a set of questions referencing feelings of anxiety currently experienced (S-anxiety) as well as items that are directed toward typical patterns of feelings (T-anxiety). The STAI has undergone several translations and adaptations and is available in many languages. There are also versions that have been created for use across the lifespan, such as the STAI for children (STAIC), and versions for use with more elderly subjects (48).

Salzman (56) measured state anxiety using a different method in an elderly sample by using a 100-mm line with anchoring adjectives. He and his colleagues used 13 such items, each with an adjective in the center (e.g., calm, nervous, jittery) and anchored with "absent" and "severe." Participants were asked to make a mark on the line indicating the degree to which they were currently experiencing the feeling. Physiological indices, including heart rate, blood pressure, and muscle action potential, can also be measured to tap activation of the autonomic nervous system due to the experience of anxiety, although differentiating anxiety (from distress or other affective states) can be difficult using only these physiological indices.

There are differences among individuals in the frequency and duration of S-anxiety. However, everyone experiences S-anxiety occasionally. Experience of S-anxiety over long periods of time and the general tendency to view the world as threatening and dangerous is used as a marker of T-anxiety (65). People who are high in T-anxiety do not constantly exhibit elevated levels of anxiety but are predisposed to exhibit anxiety when activated by a specific danger situation. For example, research has shown that people who are high in T-anxiety are more prone to perceive danger in their personal relationships and respond to these threats with greater elevations in S-anxiety than are persons who are lower in T-anxiety (65). In general, people high in T-anxiety are more vulnerable to situations that require evaluation by others because they tend to have poor self-esteem and lack confidence in themselves. High trait anxiety is associated with a lower threshold for experiencing threat or anxious affect. An inverse relationship has been found between pain sensitivity and state anxiety; the more anxious a person was (S-anxiety), the poorer the ability to discriminate varying intensities of painful stimuli (68).

The initiation and maintenance of trait anxiety have generated research suggesting that childhood relationships may contribute to the development of high levels of T-anxiety. Withdrawal of love by parental figures and negative evaluations by parents, teachers, or peers in the past may all contribute to general trait anxiety (65). However, these influences are not immutable, and T-anxiety can change. Davidson (18) investigated the effects of meditation on trait anxiety by using four groups that differed by the extent to which they were practicing meditation and found that T-anxiety was progressively lowered by extent of meditation. This was an important finding because it showed that meditation could be used to reduce the experience of trait anxiety and also because it provided evidence that trait anxiety levels can change over time.

Another model of anxiety that has received increasing attention posits self-efficacy as a key construct in anxiety. Self-efficacy theory is based on the notion that a sense of personal mastery or ability to control the environment and/or what happens to people is a primary determinant of mood and behavior (3). Self-efficacy refers to one's beliefs and expectations regarding achievement of goals; it is related to control, personal agency beliefs, and other constructs that focus on contingencies and perceived success. Changes in self-efficacy should affect mood and behavior, and evaluation of an individual's expectations provide a window on his or her motivation and likelihood of success.

Evaluations of self-efficacy are derived from several sources, including a review of one's accomplishments (taking into consideration such attributional properties as task difficulty, help received, effort, and external circumstances) and vicarious experiences such as observational learning and modeling (3). State variables, including arousal, appraisal, and social influence, may also affect evaluation of self-efficacy.

In some ways, self-efficacy is similar to self-esteem or what theorists have referred to as "self-concept." In fact, efficacy is related to both self-esteem and one's self-concept, contributing to positive esteem and overall self-perception when one's sense of efficacy is high and relatively strong. Anxiety is associated with low self-efficacy or other problems that interfere with one's perceived ability to cope with fear or with anxiety-arousing events. Avoiding feared objects may not be controlled by the fearful stimulus but rather by evaluations of self-efficacy as suggested by studies that show strong relationships between perceived efficacy and anxious behavior (e.g., see ref. 74). In these studies, covarying for self-efficacy reduced the relationship between fear and avoidance of feared stimuli, suggesting that fear and self-efficacy are distinct predictors of anxious affect and behavior.

Davison et al. (20), for example, have shown that the ratio of positive to negative self-efficacy was related to anxiety in a stressful situation, based on articulated thoughts elicited by the situation. Similarly, a study of undergraduates considering treatment alternatives for test anxiety yielded significant relationships between self-efficacy and test anxiety, though the relationship was stronger for women than for men (63).

Application of self-efficacy theory to anxiety treatment has also proven useful. Here the assumption is that anxiety reduction will be facilitated when self-efficacy is reinforced and that treating anxiety will be more difficult when evaluations of efficacy yield poor self-assessments. Behavioral achievements, verbal persuasion, information about self-efficacy, and beneficial changes in arousal detected by monitoring of symptoms of arousal are useful in increasing self-efficacy, and all of these have been used in efforts to reduce anxiety (e.g., see ref. 3). Like perceived control, self-efficacy appears to bolster one's expectations regarding success and, in doing so, increases the likelihood that one can accomplish desired goals.

Anxiety has its origins in a complex interaction of environmental, psychological, and biological events and processes. Perhaps the most critical are (a) stress and life events requiring adaptation or change and (b) early familial and school experiences.

Stress may be defined as a process linking external events, perception and appraisal of them, and responses directed at changing the event or one's relationship to it (e.g., see ref. 39). It can also be viewed as an emotional state characteristic of perception and evaluation of stressor events (e.g., see ref. 7). Stress has been defined as a nonspecific general adaptation syndrome through which we struggle to rebuff the wear and tear of life (60), whereas Cannon (14) and Mason (44) have proposed models of stress that define it as an integrated neuroendocrine response that supports our ability to cope—to fight or flee. Common to these perspectives are a shared emphasis on interactive aspects of the process or state and the purposive nature of the syndrome. Regardless of whether stress was as adaptive as Cannon (14) believed or whether it remains adaptive today, it is clear that the demands of daily life require continuous adjustment to changing surroundings and that stress characterizes some of these adjustments.

If one thinks of stress as a process, its constituents include stressors, or initiating events, and appraisal and interpretation of these stressors. Recognition of a dangerous event or situation demanding more than routine adjustment initiates an appraisal of the relevant events, the person's assets and experience, and other factors that might affect whether the event seems to be stressful. When these appraisals are benign, stress responses do not occur. However, when appraisal is not benign (i.e., when excessive demand or threat is likely), stress responses occur. These stress responses include emotional and psychological changes accompanying and following appraisal, behavioral changes, coping, and bodily responses characterized by sympathetic and pituitary–adrenal cortical arousal. Consequences of these responses, such as health changes or performance deficits, may accrue if responses are unusually intense or prolonged.

As was suggested at the beginning of this section, stress has been defined as a stimulus, a response, and a process linking them. A close listen to modern lay discussions of stress or of scientists discussing it in a research context will quickly reveal this confusing use of the word. The process view is clearly more inclusive than the others and focuses on the emotional and motivational state associated with appraised threat, harm, loss, or excessive demand. For this reason, we define stress here as the emotional experience resulting from appraisal of information about a stressor and one's ability to deal with it. This emotional state is ordinarily accompanied by physiological arousal, either as a direct co-effect of the appraisal of danger or as a part of the emotional state itself. Together these changes support one's ability to cope and motivate people to change the stressor and reduce its effects or to insulate themselves from its effects.

Viewed this way, stress is characterized by aversive emotional experience and a highly aroused state. The former is conative; if the emotional experience of stress is negative, people will be motivated to reduce or relieve it. Thus, the experience of stress motivates coping by creating tension that is aversive to the subject. This coping is, in turn, facilitated by heightened sympathetic activity, by increased circulating levels of glucose, and by other aspects of the catabolic physiological responses that occur during stress. In this way, the experience resulting from evaluation of the situation leads to a motivational and supportive arousal state that initiates further appraisal and coping (39).

Anxiety, in this context, may be seen as a component of the emotional state associated with stress and is a major part of the motivational strength of the construct. Definitions of anxiety that focus on its role as an alerting signal or indication of danger that cues mobilization of energy and resources suggest that anxiety may be an immediate affective component of stressful appraisals (6). The extent to which anxious affect becomes prolonged or intense enough to create enduring problems will depend on the nature of other aspects of the stress process. In this way, anxiety is also a sign of disorganization and dysfunction (6). Before focusing on this and other issues, the general relationship between stress and mental or physical pathology needs to be addressed.

We have portrayed stress as an adaptive process, and this is consistent with most modern models of stress. However, it is also becoming clearer that stress is an important pathological process in the development and progression of mental health problems and organic disease states. Some have suggested that modern stressors defy the "hard-wired" or biologically determined stress response because they are not readily addressed in the same ways as were stressors common as the stress process was evolving. While adaptive in many situations, stress responses include features that may not be as suitable for more "sedentary" stressors of modern life. The hyperarousal associated with stress may interfere with some coping options and may contribute to disease processes. In addition, it is possible that as stressors become more chronic, the persistence of a hyperaroused negative state may cause organic damage as well as emotional distress.

Krantz, Grunberg, and Baum (37) described three general pathways by which stress may contribute to ill health. Direct effects include physiological changes that occur as part of stress and that have specific disease-relevant consequences (e.g., increased blood pressure, reduced immunosurveillance, altered corticosteroid release). Behaviorally mediated effects are less direct: Stress may alter behaviors or motivation to perform behaviors that are healthy and/or protective against illness, resulting in possible changes in health (e.g., increased smoking or drug use, poor diet, and abnormal sleep). Finally, stress can affect the behavior of patients or people who are already ill, by increasing delay for seeking help, by causing self-medication or masking of symptoms, or by reducing adherence with medical treatment. In general, stress should not be viewed as a problem unless it becomes sufficiently intense or cumulatively burdensome to disrupt ongoing behavior. Abnormally intense or abnormally persistent stress is most likely to cause problems.

This same logic holds for the various aspects of the stress response. Psychological changes including heightened anxiety and arousal need not be viewed as a problem. Under "normal" conditions, arousal and affect are unpleasant and aversive enough to be motivating, but are not debilitating. Similarly, arousal, particularly if it is of brief duration, need not be experienced aversively. These affective changes are instrumental in increasing motivation to respond and reflect on the nature of the appraisals that are made. Resulting coping responses may be generally directed at the source of distress in attempts to reduce or eliminate its effects. Alternatively, coping may be directed inward in attempts to regulate distress and reduce unpleasant feelings.

When anxiety or any affective component of stress becomes severe, it may suppress problem-focused coping so that all effort can be focused on reducing negative affect (40). One could argue, for example, that an approaching stressor, one which we can anticipate but not predict, would be most likely to evoke apprehensiveness and anxiety. This state is then seen as contributing to the unique mixture of coping efforts that is optimal for each situation. If a stressor will be better met if one prepares for it, anxiety or apprehensiveness will be functional to the extent that it motivates anticipatory activity. However, an unusually intense anxiety response might freeze efforts at coping and focus all attention on reducing distress and fear, thereby ignoring the danger and failing to resist it. Similarly, abnormally prolonged episodes of anxious affect can predispose appraisals of subsequent stressors, limit the effectiveness of one's coping, and shape the essential experience of even routine events. Recent research suggests that individual factors, including memory, perceived control, and other variables, play important roles in maintaining stressful appraisals or responses across long periods of time (e.g., see ref. 7). Prior psychopathology or dysfunction could also increase the likelihood of prolonged distress and/or exacerbate the consequences of anxiety by intensifying the magnitude of experienced anxiety or triggering symptoms and consequences more quickly.

This theme is also present in Sarason's (57) description of an anxious person's reactions to stress, a response that includes catastrophizing, self-blame, and feelings of helplessness. To a large extent, anxiety may reflect a perceived inadequacy of resources or ability when required to act: Anxiety does not appear to obscure ability to see solutions but does increase the likelihood of perseveration, rumination, and nonproductive worrying in the face of task-related demands (57). This is also consistent with Leventhal's (40) parallel process model of emotion and predictions about overwhelming threat and responses channeled into reducing fear.

Another way of distinguishing anxiety from stress focuses on its selective and pathological aspects. Anxiety can be defined as a sense of apprehension due to perception of threat. Anticipatory responses can help prepare one for dealing with threat but carries a price in terms of distress during the pre-event period. Consistent with Lazarus and Folkman (39), nearly any and all stimuli or events are capable of posing threat or causing one to perceive the possibility of danger. The entire universe of potential threats can be broken down into those that are more likely to be viewed as a threat (e.g., tornadoes, assault, illness) and events that are less likely to evoke such an appraisal (e.g., a picnic, visiting family and friends, going to work). Those events that are likely to elicit threat appraisals can be thought of as stressors, whereas those that are less likely to cause apprehension can be viewed as anxiety stimuli when a given person reacts to them (6). While this distinction may not be as appealing as those based on other dimensions, it may provide insight into the relationships between stress and anxiety disorders.

The link between stress and anxiety is suggested by several studies of life events that show that the experience of change and the magnitude of adaptation required are related to a range of mental and physical illnesses or symptoms of illness (e.g., see ref. 32). More specifically, Johnson and McCutcheon (34) found evidence of a relationship between negative life events and trait anxiety (measured on the STAI). Adolescents were asked to indicate life events they had experienced the previous year, and rate whether each was negative or positive. Those who had experienced more life change reported more anxiety. These data are correlational, and compelling arguments can be made for all possible causal orders. However, these findings provide reason to believe that stress causes or includes anxious affect.

Anxiety can also be seen as a product of uncertainty. Life events, especially transitions, are often stressful, and the uncertainty surrounding these transitions contributes to distress and anxiety. Ambiguous situations, particularly ambiguous stressors, are associated with both uncertainty and anxiety. These situations, lacking in clear indications of situational contingencies or likely outcomes, are associated with considerable stress. The uncertainty regarding these situations highlights a lack of control that contributes to feelings of anxiety and makes coping more difficult. For example, Coelho (16) studied adolescents experiencing anxiety about the future, a stressor marked by uncertainty, finding that anxiety experienced by adolescent subjects was expressed by attempts to reduce anxiety and alter mood, much like coping with stress. These motives were often reflected in drug-taking and impulsive behavior, palliative behaviors that can lead to impaired physical health. Uncertainty regarding the future was linked with anxiety, which in turn was associated with dangerous behavior and eventual illness.

Uncertainty about an upcoming event or situation is frequently marked by anxiety. When a person is unsure about what course an event will take, they may also be uncertain as to what type of coping response will be required in order to meet the demands of the impending situation. If the event itself is unclear, there are no effective means of assessing available coping supports and identifying coping options that will be effective. This inability to "diagnose" the situation and appraise it for coping-relevant information can leave one uncertain not only about the stressful event but also about one's coping abilities.

Research on the relationship between stress and anxiety disorders is not extensive, due in part to changing diagnostic criteria and shifts in the way in which anxiety has been conceptualized. These data appear to suggest a relationship between stress and anxiety disorders but do not specify a causal path nor go beyond simple demonstration that stress and anxiety disorders co-occur. Evidence of stress as a trigger of phobic disorders, for example, is not limited to clinical reports. Several reports indicate that up to two-thirds of people experiencing phobic episodes could identify a stressful, precipitating incident. Other studies find far fewer being able to identify a trigger, and the relative role of stressor and personality factors in precipitating anxiety disorders are not clearly quantified or understood.

In some cases an individual will experience a life event that is out of the realm of normal human experience. These are referred to as traumatic events and can have substantial impact on the development and experience of anxiety. One of the most extreme reactions to a traumatic experience is seen in the anxiety disorder known as post-traumatic stress disorder (PTSD). This syndrome is marked by intrusive thoughts and reliving of the trauma, psychic numbing, hyperarousal, and sleep disturbances (2). The triggering events themselves vary and may include assault, rape, combat, disasters, and major injuries or mishaps such as motor vehicle accidents. Reactions to traumatic events vary, and most people experiencing them recover with a reasonable degree of speed and efficacy. However, some do not, and it is estimated that the lifetime prevalence of PTSD is about 1% in the general population, about 3.5% among civilians exposed to physical attack (including rape) and among Vietnam veterans who were not wounded, and up to 20% among veterans wounded in Vietnam (31). It is also estimated that as many as 55,000 individuals experience an acute PTSD response precipitated by a motor vehicle accident each year (31). Prevalence of PTSD among victims of natural disasters and technological accidents has been difficult to pin down, and its estimated range is from 2.3% to 53% (64).

Despite the fact that external stressors or traumatic events typically begin and end suddenly, the internalized event or the response to it does not subside quickly. Traumatic events usually involve several stimuli, including sights, sounds, and smells. As we know from the literature regarding conditioning, the pairing of these stimuli with the trauma lends power to the environmental stimuli that were present at the time of the event. These sounds, odors, and sights become cues for re-experiencing the traumatic event. Encountering a trigger for the traumatic event can lead to a reexperiencing or reliving of the psychological and physiological reactions that were initially elicited.

This conditioned responding is suggested by studies that have found elevated heart rates among Vietnam veteran PTSD patients when listening to combat sounds in the laboratory (e.g., see refs. 9 and 42). The intrusive thoughts and memories caused by these cues may be responsible for continued responding to the event after it occurs (7). Intrusive thoughts can be regarded as positive in the sense that a reworking and reexperiencing of the traumatic event can help a survivor to come to terms with and understand the experience. Through the intrusions and forced reconsideration of his or her circumstances, a victim can confront the actual images of the experience as well as the anxiety associated with these thoughts. These intrusive recollections may have a curative effect because through repeated exposure the anxiety may be gradually diminished (52).

Exposure to a traumatic event can lead to increased anxiety after the event and can also have long-term effects that surface with future exposure to traumatic events. This idea was noted by Freud (25) when he suggested that once a person has experienced a traumatic event and a panic state associated with the event, he/she will be more vulnerable to developing another panic state if exposed to a similar trauma; this is not unlike Horowitz' (33) notion of intrusive and avoidant phases of post-stressor distress. Once an individual has experienced a trauma-induced panic state, the occurrence of a new event that threatens injury or loss is likely to lead to a state similar to or greater than that in the past. All things being equal, this person is more likely to experience panic or distress when minimally or moderately exposed to threat than a person who had not had that previous traumatic experience.

Many studies support the association of traumatic events and anxiety. The Buffalo Creek dam collapse and flood in 1972 has been extensively examined in longitudinal field studies of responses to this sudden traumatic event (e.g., see ref. 28). Buffalo Creek survivors reported more anxiety 14 years post-disaster on both the Symptom Checklist 90 and the Psychiatric Evaluation Form (29). These survivors also had significantly more diagnoses based on the Structured Clinical Interview for DSM-IIIR than did a control population, with 18% of the sample diagnosed as having generalized anxiety disorder, 2% with panic disorder, 4% social phobia, 15% simple phobia, 23% current PTSD, and 63% PTSD-lifetime. Both the generalized anxiety disorder and PTSD diagnoses were significantly greater in the Buffalo Creek sample compared to the control group (29).

The accident at the Three Mile Island (TMI) nuclear power station in 1979 allowed for the study of responses and reactions to a technological disaster of traumatic proportion over a fairly long period of time. For 5 years after the accident, TMI-area residents reported more anxiety and exhibited greater stress-related arousal than did residents of control areas (8). Bromet (11) reported that young mothers living near TMI had an increased risk of anxiety disorders compared to those living near an undamaged plant up to 9 months post-accident. These studies provide some evidence that traumatic events, natural and human-caused, are associated with anxiety.

Not everyone who experiences a traumatic event develops PTSD or other chronic problems. A number of factors appear to be important in defining vulnerability to stress and the likelihood that it will become unusually intense or prolonged. Many of these variables have been investigated in relationship to PTSD, including coping strategies, social support, and previous psychopathology. It is important to understand what role, if any, these factors play in the development of or protection from PTSD.

As suggested earlier, stress is an emotional state resulting from appraisal of information about a stressor or one's ability to deal with it. What Lazarus (39) call "secondary appraisal" of personal coping capacity is an important component in the reaction to an experience. If an event is perceived as being outside of one's coping repertoire, the implicit inability to cope effectively can lead to a state of anxiety. In some instances a person may find that they do not have adequate coping skills to deal with a stressor, so they may turn to an alternative method of coping in order to protect their self-esteem. Coehlo (16) found that students blaming others or luck, the personality of teacher, or background to explain test results managed to conserve their self-esteem and to tolerate anxiety.

Other variables of interest in the study of anxiety disorders and PTSD include social support and the concordance of previous psychopathology with current PTSD. Research has found a positive correlation between prior psychopathology and PTSD as well as negative relationships with social support. For example, the Epidemiologic Catchment Area Survey found that nearly 80% of those people with PTSD had previously had another psychiatric disorder, but that only a third of people reporting no PTSD symptoms had ever had some other psychiatric disorder (31).

The roles of developmental or age-related changes on mood and behavior are the subjects of entire disciplines, so that one's approach to understanding lifespan influences on anxiety should be one of specifying effects and differences over the life course. The childhood environment, including one's interactions with parents and family, child-rearing practices applied, and early reactions to separation, may have long-term effects on anxiety levels. The school environment is also an important shaper of adult life, and anxieties related to academic performance, social acceptance, and one's self-concept become more important in adolescence. Adults cope with the sequelae of these previous experiences and cope with stressors and additional sources of anxiety related to career, family, security, and realization of one's dreams and goals. As one enters middle age or older adulthood, concerns may become more associated with physical health issues, and there is some evidence that fear of aging can be an important determinant of mental health.

The belief that child-rearing practices or early experience affects later behavior and personality is neither new or surprising. However, evidence of such a relationship, particularly from studies examining anxiety-related outcomes, is surprisingly lacking. Studies of repression and sensitization, for example, have not yielded evidence of a relationship between child-rearing and anxiety proneness (e.g., see ref. 13). Child-rearing antecedent conditions associated with anxiety during adolescence have been identified and include environmental factors (e.g., broken home, family conflict) as well as specific attitudes and child-rearing practices (49). Lack of clear family rules, a strong concern for a family's reputation, a poor relationship with the father, and frequent criticism and disagreement all were associated with anxiety. However, parents of children who were low or high in manifest anxiety were not different from one another on this dimension, suggesting that experiencing particular environmental and social conditions rather than having an anxious parent led to development of anxiety during early adolescence (49).

Research on child rearing and later behavior and affect is difficult for several reasons. Partly as a result, the literature on the relationship between parent–child interactions and anxiety has been inconsistent. However, some variables have begun to emerge as reliable predictors of anxiety. Parental support, child-rearing style, authoritarian personality of the mother, teachers' authoritarian attitudes, and maternal punitiveness have all been linked to anxiety in adolescence or adulthood (e.g., see ref. 38), but the only clear conclusion that can be drawn from these studies is that there are links between child rearing and anxiety that require additional investigation. Inconsistency, harsh and unyielding attitudes, ambiguity, and family conflict appear to be among the primary predictors of the development of anxiety.

Consistent with the magnitude of its impact on children, school experiences have received a good deal of attention as potential sources of anxiety. Some attention has been focused on the role of anxiety in school phobias, but most studies have considered its causes and effects on school performance (e.g., see ref. 51). Low self-concept appears to be associated with concurrent anxiety, and it may be a product of how others perceive one's academic performance (23). Other studies suggest that anxiety and self-concept have separable effects on school performance, and evidence of links between emergent anxiety and self-concept or image in social as well as academic settings in school has also been reported (22).

As one would expect, the causes and consequences of anxiety in school settings vary with age. At younger ages, when influences from parents are still stronger than those from peers, academic doubts and fears, separation from parents, and similar concerns appear to be related to anxiety (36). As they grow older, children become increasingly aware of peer influences as well, and the influence of these sources of anxiety increase (1). Anxiety in this context may be viewed as a complex of experiences including how parents react to early achievement motivation, children's ability to interpret their performance and compare it to others, and their reactions to evaluative practices applied in school (73).

It should be noted that anxiety due to particular aspects of school performance have been examined in some detail. For example, math anxiety, related specifically to performance at mathematics, does not necessarily generalize to other aspects of school (66). Similarly, test-taking anxiety, which clearly has very broad implications for students, and computer anxiety, of increasing concern during the past decade, have received attention (57). Review of the literatures on these topics is beyond the scope of this chapter, but these and other specific sources of anxiety in school settings have been considered as targets for interventions to improve school performance.

Anxiety and anxiety disorders are common in the elderly, in part due to concerns and worries about bodily symptoms and changes in health (41). Fear of aging is one antecedent condition of anxiety in some, though worries about aging may occur across the entire adult life cycle. Some of this is related to the fear of death and dying, as suggested by Vickio and Cavanaugh (70), who studied 133 nursing home employees across a range of ages and jobs. Results indicated that increasing fear of death was associated with more anxiety toward aging. For the most part, however, most attention in this area has been on treatment rather than etiology, with concerns about drug interactions and synergistic effects of drugs and declining cognitive resiliency (61). It seems likely that in a population marked by increasing concerns about one's health, changes in bodily sensations would evoke more worry and apprehensiveness, and this alone could yield higher rates of anxiety and dysfunction among older people than among younger ones (decreases in other causes could offset these increases). Etiological changes in anxiety disorders over the lifespan would suggest more targeted pharmacologic and nonpharmacologic interventions.

The distribution of anxiety disorders in populations, as revealed by epidemiological and twin studies over the past 25 years, suggests strong familial patterns and genetic–environmental interactions in the etiology of these disorders (e.g., see refs. 17 and 72). In general, this is consistent with broader findings for affective disorders, indicating that close relatives of patients are more likely to share disorders and that nearly two-thirds of monozygotic twins are concordant for particular disorders (27). Though limited by the nature of the variables assessed in these epidemiological studies, there now appears to be considerable evidence for genetic determination of some aspects of anxiety. Investigation of 215 probands (including 82 controls, 52 patients with major depression, 51 patients with major depression and anxiety disorders, and 30 patients with anxiety disorders only) and more than 1500 adult and child first-degree relatives has provided further evidence of familial influence (72). First-degree relatives of the 51 probands with both depression and anxiety were generally more likely to show major depression and anxiety disorders than were relatives of patients with major depression alone. Similarly, relatives of patients with anxiety disorders that were not associated with major depression showed higher rates of anxiety disorders than did relatives of patients with major depression or with no diagnosis. It is important to note, however, that the rates of dysfunction among these relatives were relatively low: For anxiety disorders, relatives of normals showed a rate of 5 in 100, relatives of patients with major depression were somewhat more likely to experience anxiety disorders (9/100), and among patients with anxiety disorders with or without depression, 14 or 15 of 100 relatives exhibited anxiety problems (72). Though these rates suggest that most relatives of patients with these disorders did not exhibit symptoms of anxiety or depression, they suggest that relatives of patients with anxiety disorders were more likely to show symptoms of similar dysfunction (72).

The causes of such familial patterns are unclear. Genetic predispositions are indicated as potential mechanisms, either as direct tendencies to develop symptoms of anxiety or as physiological or biochemical predispositions to respond to environmental events in particular ways. Examination of shared patterns of response to drugs, to external events, and to other stimuli may provide important information about the underlying bases of inherited risk for anxiety disorders. Differences in cardiovascular or sympathetic reactivity, implicated in the development of hypertension and sociopathy, may be one such mechanism. Research has not systematically addressed these possibilities, and future investigations could include response by gamma-aminobutyric acid (GABA) and responses to benzodiazepines as well as interaction of genetic and behavioral history factors as described by Barrett (5). Similarly, activity of endogenous opioid peptides as well as exogenously applied opiates may vary across individuals. The point here is not to catalog the various systems and neurotransmitters involved in anxiety so much as to suggest points at which inherited predispositions may make a difference in the development of anxiety. Experimental induction of anxiety, by administration of drugs or by enforcing withdrawal from them, may offer one way of identifying genetic–environmental interactions.

Sheehan and Soto (62) have suggested that research and treatment of anxiety disorders will be facilitated by conceptualization of anxiety and associated dysfunction as either exogenous or endogenous. This distinction rests on the notion that some anxiety and anxiety disorders are caused by, or are sensitive to, environmental changes and stimuli outside the organism. Others, related to internal causes and events, are endogenous and more resistant to behavioral treatment (62).

Our focus in this chapter has been on exogenous anxiety with emphasis on the environmental factors responsible for the etiology and course of anxiety and anxiety disorders. Exogenous anxiety may be manifest in simple phobias, where responsiveness is limited to a single stimulus, and in adjustment disorders accompanied by anxiety (62). Exogenous anxiety is also involved in the development of PTSD, where anxiety and distress are linked to profound stressors and to stimuli reminiscent of these stressors. Stress, whether early in development or during adulthood, appears to be an important process in the experience and expression of anxiety, and though more work is needed to address the role of stress in dysfunctional anxiety, it also appears to be an important factor in anxiety disorders. Under benign conditions, anxiety appears to serve an alerting function, keying an alarm reaction and letting the organism know that something is wrong. Also under these conditions, anxiety may be a principal component of the stress experience and may play a major role in motivating the organism to act to decrease or eliminate distress. However, when stress is unusually intense or prolonged the functional nature of anxiety may diminish and, because it no longer motivates effective coping and tension reduction, may become abnormally intense or persistent. When this occurs, and when anxious affect begins to cause dysfunction and interference with daily life, anxiety disorders develop and require effective management and treatment.

published 2000