To better understand anxiety, it is helpful to take a closer look at the fear response. Fear is a normal response to a threat, whereas anxiety is an unwarranted or inappropriate fear [4]. Anxiety and fear do not have to be learned. They are unconditioned, protective responses. The fear/anxiety response includes defensive behaviors, arousal of the autonomic system, increase in somatic reflexes, and activation of the hypothalamic-pituitary-adrenal axis [4].

Several parts of the brain are involved in fear and anxiety. Neurochemical studies and brain imaging techniques have improved the understanding of the complex network of interacting structures responsible for these emotions [7]. The cerebral cortex and the amygdala are two major brain areas involved in the perception of a threat. The cortex is the thinking or cognitive portion of the brain. The amygdala is an almond-shaped structure that serves as a communications center for the parts of the brain that process incoming sensory signals and interprets the information. It is involved in rapid, automatic responses that prepare the brain and body to deal with danger and the unexpected [3]. The fear response via the amygdala occurs before the cortical response, and so the response may be “automatic” without the individual having time to actually think about any action. The amygdala can register the presence of a threat, trigger a fear response or anxiety, and store emotional memories [7]. Various anxiety symptoms may occur including an increased startle response, hypervigilance, shortness of breath, and a facial expression of fear [4]. Increased output from the amygdala is common with the anxiety disorders.

The body’s response to a threat also involves the activation of the hypothalamus, which serves as a command center for the hormonal and nervous system of the body [3]. Neurotransmitters are chemical messengers within the brain, and hormones carry messages throughout the body. The hypothalamus releases corticotropin- releasing factor (CRF) that triggers the release of adrenocorticotropic hormone (ACTH) from the pituitary gland. Adrenocorticotropic hormone stimulates the release of cortisol from the adrenal gland. This stress hormone is released into the bloodstream and has a regulatory effect on the brain, maintaining physiologic integrity. Cortisol is involved in complex negative feedback loops [14]. Excessive and sustained secretion of cortisol, however, can lead to adverse medical effects [14]. The adrenal medulla has direct communication with the brain by way of the sympathetic nervous system. The release of catecholamines prepares an individual for the “fight or flight” response by causing such responses as an increased heart rate and blood pressure, a diversion of blood from the internal organs to the muscles, increasing alertness, and increasing glucose to provide energy.

The hippocampus is a brain structure that processes traumatic stimuli and helps to encode the information into memories. Associated cues are stored in the hippocampus, and these may allow an individual to avoid stimuli that may trigger emotional trauma in the future [4]. Studies have shown that the hippocampus appears to be smaller in patients who have suffered severe stress such as combat or child abuse [7].

Cognitive control of anxiety occurs in the medial frontal cortex that is connected to the amygdala. This allows an individual rationally to evaluate a situation, regulate affect, control behavioral and interpersonal responses, and modulate autonomic and neuroendocrine function [3, 4]. If the stressors are particularly challenging, the lower centers such as the amygdala take over from the executive centers in the prefrontal cortex [4]. When a person suffers from an anxiety disorder, the response tends to be limited to the amygdala-mediated pathways, which can be pathological. Different parts of the amygdala may be activated with the different anxiety disorders and results in different manifestations of anxiety [3]. For example, individuals with panic attacks have a fear of dying. Free-floating anxiety is common with generalized anxiety disorder. Fear of embarrassment is a typical symptom with social anxiety disorder. Intrusive obsessions are common with obsessive-compulsive disorder. Emotional memory is common with posttraumatic stress disorder [4].

There are several other brain structures involved in fear and anxiety. These include the cingulate, basal ganglia, and striatum. Life-threatening traumatic experiences can be etched into the amygdala. New favorable memories can decrease more threatening memories. However, new traumatic experiences or associations can trigger original, unfavorable experiences [4]. Anxiety tends to occur with limited patterns of thinking and behavior and is associated with circuits that are emotionally driven [4]. The fear response, therefore, can be automatic and lifesaving in situations of real danger. On the other hand, the anxiety response, as part of a learned fear response, may be an overreaction to a relatively benign situation that can be problematic and can perhaps be disabling. A core problem in anxiety disorders is a faulty connection between a stimulus and a response as well as a misinterpretation of an event’s meaning [3].