Anxiety

Anxiety refers to that uncomfortable feeling of apprehension or dread with which we are all familiar. It is similar to fear but differentiated from it by some writers by the inability of the anxious person to identify clearly what it is he is apprehensive about. Intense anxiety is usually accompanied by easily identifiable physiologic changes such as palpitation, sweating, pupillary dilation, and tremulousness. These account for some of the physical discomfort we subjectively associate with anxiety. Intense anxiety may have a disruptive effect on purposeful behavior; indeed, one method of detecting the presence of anxiety and changes in its intensity is to observe its effects on ongoing behavior. This aspect of anxiety, its environmental origins and effects on the operant repertoire of the individual, is discussed in detail later in the text (see Chapter 15).

Anxiety is of importance in the understanding of behavior for several reasons. It is a frequent complaint of patients and can be seen, in varying degrees of intensity, in most psychiatric disorders. In addition, much of human behavior we call "emotional," as well as that we call "neurotic," may be regarded as the result of intense anxiety. Thus, the behavior of the chronic alcoholic of drinking excessively may be maintained, in part, by the effect of alcohol in reducing anxiety. Similarly, some neurotic habits such as compulsive hand washing or avoiding certain streets may owe their strength and persistence in part to their effect of reducing anxiety.

Anxiety is pathologic or harmful only when excessive or inappropriate. Its presence in normal persons and its role in the growth and development of personality is discussed in Section II. The present section will deal mainly with some biologic aspects of anxiety.

It has been known for some time that severe physical stress, such as that produced by burning, intense electric shock, or surgical trauma, brings about a greatly increased outflow of steroids from the adrenal cortex. Psychologic stress is also a powerful stimulus for adrenocortical outflow as demonstrated by laboratory animals placed in situations of conflict or situations requiring important decisions (46). The potency of a psycho-logic stress in eliciting an adrenocortical response is demonstrated in an experiment by Brady and his associates (12, 13). In this experiment, one group of rats received, at random intervals, an electric shock which was always preceded by a buzzer. After several pairings of the buzzer and shock, the buzzer alone - a preaversive stimulus - provoked behavior suggestive of intense anxiety in the animals. The rats showed varying degrees of adrenocortical exhaustion and several died. A control group, which received shock of the same intensity and frequency but not preceded by a buzzer, the warning signal that induced additional anxiety in the first group, showed less marked changes and none died.

The relationship of adrenocortical function to anxiety has been extensively studied in human subjects, especially since improved methods of biochemical assay and direct chemical measurement of endocrine products have become available. Although there are many chemically different, biologically active principals secreted by the adrenal cortex in man, the plasma level of hydrocortisone has been most studied with respect to changes in mental state. Many laboratories have reported a significant increase in plasma hydrocortisone level in emotionally disturbed patients in whom anxiety is the common denominator (7, 55). Significant elevations have been reported also in urinary hydroxycorticoid and 17-ketosteroid excretion, metabolites of hydrocortisone and indices of adrenocortical activity. Finally, the blood level of pituitary corticotropins, which stimulate the release of adrenocorticoids, has been found elevated in anxious patients (59). Elevations in these indices of adrenocortical function have been produced also in normal subjects in whom anxiety was experimentally induced by various procedures (44, 56, 57, 58). Anxiety has been experimentally induced in normal subjects by such means as stressful interviews and giving the suggestion of anxiety to hypnotized subjects (43). In many of these studies the amount of hydrocortisone elevation has been correlated with the degree of anxiety as assessed by various clinical and psychologic means.

Recently it has been shown that inducing a state of deep calm and relaxation, as by showing subjects motion pictures of a tranquil, pastoral nature, causes a drop in plasma hydrocortisone levels below usual baseline values for the particular time of day (32).

There is some evidence, although less clear-cut, that the plasma hydrocortisone level is higher than normal in chronically depressed individuals as well (8, 51).

The elevated level of plasma hydrocortisone observed to accompany anxiety could be the result of an absolute increase in the adrenocortical release, decreased rate of disposal and clearance from the blood, or some combination of these. The observation that urinary metabolities of hydrocortisone, such as hydroxycorticoids and 17-ketosteroids, are increased in anxious individuals suggests that the principal mechanism is increased production and release of the hormone. To test for the possible role of differences in utilization rate, however, Persky (53) administered test loads of hydrocortisone (1 mg. per kg. body weight) to anxious patients and non-anxious controls. The hydrocortisone was found to be cleared more rapidly in the anxious patients than in the non-anxious control subjects. Among the patients, the rate of disappearance was proportional to the degree of anxiety present. Thus it appears that anxiety is associated with elevated plasma hydrocortisone despite a more rapid rate of disposal.

Since production and release of hydrocortisone from the adrenocortex occurs in response to stimulation by pituitary corticotropins, the elevated plasma hydrocortisone seen in anxiety might be the result of absolute increase in corticotropin production or an increased sensitivity of the adrenocortex to the tropic hormone. Evidence of an absolute increase in corticotropins such as ACTH has already been mentioned. To explore the possibility of increased sensitivity as a factor, Persky (54) administered single 15 U.S.P. unit doses of ACTH to normal subjects and anxious patients. Significant differences were not found in the two groups in the plasma hydrocortisone levels that resulted. However, on administering progressively larger doses to two similar groups of subjects on three consecutive days, the plasma hydrocortisone level of the anxious group was higher than that of non-anxious controls. These data suggest an increased responsiveness of the adrenal cortex in anxious individuals to the stimulating effects of corticotropic hormones.

In summary, then, a variety of changes in adrenocortical function occur in anxious individuals. These include increased production of ACTH, increased responsiveness of the adrenal cortex to ACTH, elevated plasma hydrocortisone, and increased utilization or disposal of hydrocortisone. The role of increased hydrocortisone which occurs following physical trauma has a variety of reparative functions. The role of the hydrocortisone following psychologic stress is less clear, however. Two recent experiments throw some light on this issue. Wiener and his associates (72) administered hydrocortisone intravenously to a group of normal medical students and, on another occasion, an equal volume of saline placebo solution to the same group. Although the subjects reported no subjective differences under the two conditions, not knowing which was hydrocortisone and which placebo, and no evidence of overt anxiety was observed, the subjects' responses to psychologic tests suggested an anxiety-proneness following the hydrocortisone infusion. In a related experiment, Levitt and his associates (44) studied the effects of an anxiety-provoking stimulus, the suggestion of anxiety under hypnosis, to normal subjects primed with intravenous hydrocortisone and normal subjects receiving a saline placebo infusion under the same conditions. Although no differences were observed in the intensity of the anxiety that resulted, the anxiety in the group primed with hydrocortisone was more protracted and was terminated with greater difficulty than in the group not primed with hydrocortisone. These latter researchers suggest that hydrocortisone may play some role in the production of anxiety and that the anxiety produced may in turn influence adrenocortical activity. Further research is required, however, to elucidate these mechanisms.