anxiety is an emotional state, represented by a feeling of dread, apprehension, or fear. In humans, this can be defined by description using language; in animals, it must be inferred from behavioural observations. Tests of anxiety in man are thus based on self report, and these may be divided into features that characterize the person's temperament (
‘trait’ anxiety) or that describe a current emotional state (
‘state’ anxiety). In animals, it is inferred by the animal's response to an anxiety-provoking situation such as a threatening environment. Distinctions between anxiety and other emotional states, such as fear or even ‘arousal’, are not always clear. Also, there are close associations between cognition and
emotion: man has the capacity not only to know, but also to respond emotionally to what he knows.
However, anxiety is not only a behavioural phenomenon. Characteristic autonomic changes take place, typically including increased heart rate and/or blood pressure. There is also marked endocrine activation, particularly increased secretion of the adrenal hormones
adrenaline (and
noradrenaline) and
cortisol (the ‘
stress’ hormone). There has been much discussion of how far these ‘peripheral’ events can actually induce emotional states such as anxiety, or are part of the body's response to those states. Current opinion puts most emphasis on ‘central’ instigation (by neural mechanisms), though it may be true that accentuated autonomic activity can elicit emotional states, especially when there is a perceived rationale for such activity — ‘cognitive labelling’. Persistent changes in certain hormones (for example, cortisol) may alter the ability of an individual to respond anxiously to provoking stimuli.
Biologically, anxiety has a prime function in adapting to, or avoiding, threatening situations. In animals, one of many ways of inducing such a presumed response would be by pairing a neutral stimulus (say, a light) with a consequent aversive stimulus (such as a footshock). After several such pairings, presentation of the light alone will result in the behavioural and physiological features of anxiety. Similar features can be elicited by exposing animals to situations that they find naturally threatening, such as strange surroundings, or physical peril. This implies that a state of high anxiety is aversive — borne out in humans by the demand for drugs that reduce it, and in animals by showing that they will work to reduce their anxiety levels. Because animals and people find anxiety aversive, they will avoid those circumstances that give rise to it, and hence the threat itself. ‘Fear’ can be substituted for ‘anxiety’ in many of these contexts.
Anxiety can, therefore, be the result of stimuli which are naturally threatening (for example the response of a rat to the presence of a cat), those that have been associated with previous danger (the surroundings where the cat is found), or stimuli that are not in themselves threatening, but have become so because of a learned association between them and subsequent discomfort or threat.
Clinically, if significant or disabling levels of anxiety occur without there being sufficient apparent cause, either current or past, then the patient is said to suffer from an
anxiety disorder. These disorders can be ‘global’, or generalized, in those people who have high levels of anxiety without evident provoking events; or they can be ‘specific’, where high anxiety is induced by circumstances which, for most people, would not be considered
anxiogenic (such as open spaces, spiders, meeting people) — these are sometimes termed ‘phobias’. In some cases, anxiety occurs in sudden waves (‘panic attacks’). Anxiety may also occur as part of another medical condition, or as one result of a drug of abuse or a medication.
Post-traumatic stress disorder is a particular form of anxious attack provoked by involuntary recall of a previously life-threatening episode (usually triggered by some salient stimulus; for example the sound of a helicopter in those traumatized by war). Psychoanalytical theory has been much concerned with the causes and meaning of individual differences in anxiety.
Attempts have been made to define particular parts of the brain that may be responsible both for physiological or pathological anxiety. There is general agreement that damage to the
amygdala can reduce anxiety, both that which is a response to ‘natural’ stimuli and that generated by learned associations. The amygdala (or
amygdaloid complex, or
nucleus) is a collection of grey matter that is part of the limbic system, situated in each temporal lobe of the brain, between the cerebral cortex and the hypothalamus. It consists of a number of sub-components (
nuclei), and some evidence is emerging that different nuclei in the amygdala may play defined roles in certain forms of anxiety. Electrical or chemical stimulation of the amygdala may induce anxiety-like states. There are those who think that the principal or only role of the amygdala is to generate fear or anxiety-like states, but it is more likely that this is one special case of a more general role for this part of the brain. Humans with congenital damage to the amygdala may also have difficulty, for example, in recognizing emotionality, such as fear, in others, or the emotional content of stories.
Scans of the brain by
magnetic resonance imaging (MRI) show that the amygdala is activated by stimuli that induce or represent emotional states, including fear or anxiety. However, MRI and other imaging techniques have also shown many other parts of the brain to be activated in anxiety states, depending on the condition being studied, or the way in which anxiety is generated; these include parts of the cortex of the frontal lobes, known to be involved in emotional responses, and closely associated cortical areas. There are many connections between the amygdala and these areas of cortex. There is some evidence in the human brain for asymmetry in the role of the frontal cortex: the right side may be particularly important in aversive emotional states such as anxiety.
A number of chemical systems in the brain have been implicated in anxiety. The discovery that the
benzodiazepine drugs (e.g. librium, valium) had major and quite specific anxiety-reducing (
anxiolytic) effects on both humans and experimental animals prompted the search for chemicals in the brain that might regulate anxiety levels. Benzodiazepines act by antagonizing the neurotransmitter
GABA (
γ-amino-butyric acid), a compound widely used by nerve cells in the brain to inhibit the activity of other nerve cells. Why this should result in a specific effect on anxiety remains an enigma. At one time, many millions of prescriptions for benzodiazepines were written each year, but it has now become apparent that persistent use may have undesirable side effects, including rebound anxiety once they are discontinued. They nevertheless remain a staple treatment for anxiety disorders. Drugs acting on other systems also have clinically useful anxiolytic effects; these include drugs that modify the action in the brain of
serotonin or of
noradrenaline. Both serotonin and noradrenaline are activated in the brain by anxiety-inducing circumstances.
More recently, certain
peptides in the brain have been shown to be involved in anxiety. One is
corticotrophin-releasing factor (CRF). This peptide, when infused into the brain of an experimental animal, results in anxiety-like behaviour, as well as the other physiological signs of anxiety. CRF acts on specific receptors on neuronal cell membranes in the brain. These have been shown to be responsible for its anxiogenic actions, because drugs that block CRF1 receptors, or animals that are bred without these receptors (
CRF1R-deficient transgenic mice), show reduced anxiety. CRF antagonists may, therefore, be the precursors of a new generation of anti-anxiety drugs. However, CRF has other behavioural effects, including actions on food intake and sexual behaviour, and it remains to be established whether other categories of receptors are responsible for these various roles. It is also not clear whether anxiety disorders can be related to inappropriate amounts of these normal neuropeptides, or to the presence of abnormal molecules.
J. Herbert
Bibliography
Davis, M. (1992). The role of the amygdala in fear and anxiety. Annual Review of Neuroscience, 15, 353–75.
Le Doux, J. E. (1995). Emotion: clues from the brain. Annual Review of Psychology, 46, 209–35.
LeDoux, J. E. (1998). The emotional brain. Weidenfeld and Nicolson, London.
See also
conditioning;
peptides;
membrane receptors;
stress.
