The discovery that the benzodiazepines bind to specific sites of the GABA receptor complex and that the sedative and amnesic effects (α1 subunit) of these drugs seem to be separable from their anxiolytic effects (α2 subunit) raises the possibility that abnormalities of the GABA system directly underlie anxiety. However, there is only indirect evidence for this mechanism. Of potentially greater importance is the finding of genetic polymorphisms that relate statistically to the presence of anxiety states, such as one in the serotonin transporter gene (Lesch et al). It has been estimated that allelic differences on the chromosome contribute perhaps 10 percent to the overall anxiety tendency. One presumes that there are numerous additional genes that participate in a similar way. Others have not found this particular association or have found it only in patients with generalized anxiety and not in those with panic attacks. Consequently, the precise relationship of genetic polymorphisms to anxiety states cannot be stated at this moment, but a heritable component is undoubted.
Shorn of the psychologic components of apprehension and fear, the anxiety and panic attack consists essentially of an excessive autonomic, mainly sympathetic, discharge. Some of the autonomic symptoms are therefore duplicated by pheochromocytoma. The prominence of chest discomfort and respiratory distress during an acute anxiety attack may be mistaken for myocardial ischemia, in which case the patient is often subjected to a series of studies of cardiac function. Another form of the illness—in which nondescript dizziness, vague difficulty with visual clarity, and fear of losing consciousness are the most prominent features—may be mistaken for an vestibular problem (see “Nonvertiginous Types of Dizziness” in Chap. 14) or for epilepsy. In contrast, headache is (surprisingly) a relatively infrequent experience and the diagnosis should be suspect if it is a prominent feature. Other medical diseases that may be brought to mind by isolated elements of an anxiety state are pulmonary embolism, cardiac arrhythmias, hypoglycemia, hypoparathyroidism, alcohol, drug, nicotine withdrawal and especially, complex partial seizures. The autoantibody syndrome associated with NMDA antibodies and some instances without these antibodies may have anxiety as its opening feature. In regard to seizures as imitators of anxiety, however, loss of consciousness, incontinence, and clonic or myoclonic movements do not occur in anxiety spells. Adherence to the diagnostic criteria of these disease states readily permits their differentiation from acute anxiety, but diagnosis may be difficult if the symptoms are brief.
Of equal importance is the relationship of anxiety to depression. A large proportion of patients with depression have symptoms of anxiety. Indeed, some psychiatrists believe that anxiety neurosis is accounted for mainly by a variant of depression. As has been mentioned, an anxiety state appearing for the first time after the 40th year usually proves to be primarily a depression, although it may be that a predisposing personality trait is involved. The presence of symptoms such as overwhelming fatigue, self-deprecation, and feelings of hopelessness and, of course, ideas of self-destruction makes depression the fundamental diagnosis, with anxiety an associated feature (anxious depression). As mentioned, a very small number of patients with a condition diagnosed as pure anxiety neurosis have committed suicide, but this does not hold if depression is the central illness.
Schizophrenia may also begin with prominent anxiety symptoms. Here the diagnosis rests on finding the characteristic thought disorder of schizophrenia, which may emerge only with time and after several interviews. Hysteria may include anxiety symptoms, though they are seldom prominent, and phobic and obsessive-compulsive neuroses constantly create an anxious state in affected patients, but each has distinguishing attributes.