A term to describe the physiological and psychological response to a perceived threat that can represent either a biologically appropriate adaptive response to impending challenge or a pathological state whereby there is a contextually and temporally inappropriate activation of bodily defence systems. When anxiety is chronic and appears to be dissociated from defined threat events, it is generally considered to be abnormal and to merit psychological or psychopharmacological (see PSYCHOPHARMACOLOGY) therapeutic intervention. Contextually appropriate anxiety is considered as an integral component of the FIGHT-OR-FLIGHT response. The main clinical features of anxiety can be divided into two categories, cognitive and physiological. Typical cognitive features include apprehension, perception of impending threat and constant vigilance for danger. Typical physical features include increased AUTONOMIC NERVOUS SYSTEM activity with elevated heart rate, respiratory rate and blood pressure. There is also an elevated release of stress hormones from the adrenal glands, such as ADRENALINE and cortisol (see CORTICOSTERONE).
There are three major subdivisions of the so-called clinical anxiety disorders, although anxiety symptoms are ubiquitous throughout the entire range of psychiatric diagnoses. (1) GENERALIZED ANXIETY is a term used to describe a global, non-specific, persistent anxiety without the specific features of PANIC disorder or PHOBIA. (2) Panic disorder is characterized by recurrent attacks of acute, severe and overwhelming anxiety accompanied by sensations of breathlessness, cardiac palpitations and dizziness. There is often an acute fear of losing consciousness, or even of dying. Such attacks may become associated with specific predictive stimuli such as places, leading to marked anticipatory fear and an avoidance of these locations. (3) PHOBIC ANXIETY is that generated by very specific stimuli in an irrational, involuntary manner, leading to significant avoidance behaviour. Common phobic stimuli include spiders and social situations. Clinically, there is significant overlap among the three categories of disorder.
Anxiety symptoms appear to be mediated by a complex neural circuitry that includes multiple components of the LIMBIC SYSTEM. Enquiry into the neural basis of anxiety has traditionally taken three main approaches. First, to investigate the mechanism of action of drugs known to suppress or alleviate anxiety symptoms. Second, to develop ANIMAL MODELS OF ANXIETY or of FEAR (see CONDITIONED FEAR) which are sensitive to the ANXIOLYTIC (anxiety reducing) effects of drugs. Third, to describe the neural pathways and chemical systems activated by fear stimuli and to develop specific drugs to act on those systems. Advances in brain imaging techniques have added a further option for the detection of which structures and chemical systems are activated by fear stimuli in humans. For example, changes in cerebral blood flow patterns and some structural changes have been demonstrated in the anterior TEMPORAL LOBE, specifically in the PARAHIPPOCAMPAL GYRI, in panic disorder patients when anxiety is experimentally induced. Similarly, the ORBITOFRONTAL CORTEX has been identified as a likely site for pathology in patients with OBSESSIVE-COMPULSIVE DISORDER, a clinical syndrome that is considered by many to represent a specific type of anxiety disorder. The amygdaloid complex also appears to be a critical substrate for the mediation of fear and anxiety. Anatomically, the AMYGDALA is well placed to integrate many of the physiological responses typical of states of fear or anxiety, with prominent projections to the HYPOTHALAMUS, LOCUS COERULEUS, the VENTRAL TEGMENTAL AREA (VTA) and multiple BRAINSTEM nuclei involved in autonomic control. Electrical stimulation of the central nucleus of the amygdala elicits complex behavioural and autonomic responses that closely resemble those observed during states of fear. Furthermore, a LESION of the central nucleus of the amygdala can lead to an abolition of the integrated behavioural and physiological responses to stimuli which have previously been paired with aversive events, a so-called CONDITIONED EMOTIONAL RESPONSE. However, amygdala lesions do not closely mimic the effects of anxiolytic drugs.
Animal models of anxiety are conventionally grouped into those which are based on PUNISHMENT, reward reduction, or those with an ethological perspective. Typical tests based on punishment include the GELLER-SEIFTER CONFLICT test, where an aversive stimulus, e.g. an electric shock, is used to suppress a rewarded behaviour, such as lever-pressing for food. A typical test based on reward reduction is that of the negative contrast, where two rewards of differing magnitude are juxtaposed and the response to the reduction is measured. The most widely used ethologically based tests include the ELEVATED MAZE where patterns of activity on the apparatus are deemed to reflect competition between EXPLORATION and avoidance. Each of these tests appear to detect anxiolytic drug action quite reliably (see BENZODIAZEPINE).
