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thalamus, raphe nuclei, nucleus ceruleus, and other regions of the brainstem); blocking such activity by drugs or by destruction of the amygdala eliminates anxiety and fear-like behavior Admittedly the concepts of fear, stress, and anxiety are used interchangeably in these models, but repeated stimuli that produce fear and stress may eventually induce a state akin to anxiety, and the amygdala appears to be involved in the perpetuation of this anxiety state The meaning of these effects, ie, whether they are primary or secondary, is not certain, but it is evident that prolonged and diffuse anxiety is associated with certain biochemical abnormalities of the blood and probably of the brain In addition to the role of the amygdala, animal studies have related acute anxiety to a disturbance of function of the locus ceruleus and the septal and hippocampal areas the principal norepinephrine-containing nuclei It is noteworthy that the locus ceruleus is involved in rapid-eye-movement (REM) sleep and that drugs such as the tricyclic antidepressants and monoamine oxidase inhibitors, which suppress REM sleep, also decrease anxiety Certain of the serotonin receptors in the brain, different from those implicated in depression, have been related to anxiety Other parts of the brain must also be involved; bifrontal orbital leukotomy diminishes anxiety, possibly by interrupting the medial forebrain connections with the limbic parts of the brain Positron emission tomography (PET) studies in subjects who anticipate an electric shock show enhanced activity in the temporal lobes and insula, implicating these regions in the experience of acute anxiety (see also page 444) Other credible studies have demonstrated a role for the anterior cingulate gyrus in eliciting many of the autonomic features (particularly increased heart rate) of excessive arousal and anxiety Several other alterations in neurotransmitter function have been implicated in the anxious state The nding that a small proportion of the inherited personality trait of anxiety can be accounted for by one polymorphism of the serotonin transporter gene is provocative (Lesch et al) but requires further study Anxiety, being so ubiquitous, is probably not without biologic signi cance It strengthens social bonds at certain moments in life, among men in combat, for example, or when there is a threat of separation of child and mother (separation anxiety); in the adult period, anxiety can help to stabilize marriage, companionship, and work Also, intense intellectual activity can be facilitated by controlled amounts of anxiety Barratt and White found that mildly anxious medical students performed better on examinations than those lacking in anxiety As anxiety increases, so does the standard of performance, but only to a point, after which increasing anxiety causes a rapid decline in performance (Yerkes-Dodson law).

when repeatedly frustrated by threats that they cannot control Human beings forced to work under con ned conditions and constant danger and cultural groups removed from their home and traditional way of life lose their coping skills and suffer anxiety and depressive reactions Presumably they have an increased output of stress hormones (cortisol and adrenaline) Such psychologic disorders, bearing a direct relationship to environmental stressors, are among the most common occupational health problems One such stress syndrome, in which an individual develops delayed or recurrent symptoms of anxiety after exposure to extreme psychologic trauma, has been given its own name posttraumatic stress disorder (PTSD) Stress syndromes are distinguished from anxiety neurosis, in which the psychologic disturbance arises from within the individual and has no de nite relationship to environmental stimuli Whether certain individuals are by nature hyperresponsive to such stimuli is not known The only therapeutic approach is to attempt to alter the patient s perception of stress for example, with psychotherapy and meditation exercises and to remove him, if possible, from recognizable environmental stressors (See Editorial in References)

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The phenomenon of irritability, or an irritable mood, must be familiar to almost everyone, exposed as we are to all of the noise, niggling inconveniences, and annoyances of daily life It is, nevertheless, a dif cult symptom to interpret in the context of psychopathology Freud used the term Reisbarkeit in a restricted sense to denote an undue sensitivity to noise and considered it a manifestation of anxiety, but obviously this symptom has a much broader connotation and signi cance For one thing, some people are by nature irritable throughout life Also, irritability is an almost expected reaction in overworked, overwrought individuals, who become irritable by force of circumstances An irritable mood or feeling may be present without observed manifestations (inward irritability), or there may be an overt loss of control of temper, with irascible verbal and behavioral outbursts, provoked by trivial but frustrating events Irritability in the foregoing circumstances can hardly be considered a departure from normal However, when it becomes a recurrent event in a person of normally placid temperament, it assumes signi cance, for it may then signify an ongoing anxiety state or depression Irritability is also a common symptom of obsessional neurosis Here the irritability tends to be directed inward, indicating perhaps a sense of frustration with personal disability (Snaith and Taylor) Depressed patients are frequently irritable; as a corollary, this symptom should always be sought in patients suspected of being depressed, since it is so readily recognized by both patients and their families The days preceding menses and the mother s common postnatal mood disorder are characterized by high levels of outwardly directed irritability Short-temperedness and irritability are also common features of the manic state The most extreme degrees of irritability, exempli ed by repeated quarrelsome and assaultive behavior (irritable aggression), are rarely observed in anxiety neurosis and endogenous depression but are usually the mark of sociopathy and brain disease Such irritable aggression is also observed in some patients with Alzheimer disease and other types of dementia and following traumatic contusions of the temporal and frontal lobes.

The psychologic phenomenon of stress is closely allied to nervousness, fatigue, and anxiety, and all of them are pervasive features of modern life In general terms, stress has been de ned as a feeling of self-doubt about being able to cope with some situation over a period of time The term stress syndrome refers to perturbations of behavior and accompanying physiologic changes that are ascribable to environmental challenges of such intensity and duration as to overwhelm the individual s adaptive capacity The biologic effects of this phenomenon can be recognized in many species chickens laying fewer eggs when moved to a new coop and cows giving less milk when put in a new barn, or monkeys going berserk

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