Stress is the simple name for what happens when the body's emergency response is activated; a stressful event is one that activates the sympathetic (fight-or-flight) nervous system. Because it elevates arousal, heart rate, and breathing, stress is useful for helping animals and humans escape dangerous situations; however, it can damage the body to be under stressful conditions for too long.

The HPA and Stress

Stressors can come in many forms, from immediate physical threats like an angry bear, to social threats like an angry friend. In experimental studies in rats, a distinction is often made between social stress and physical stress, but both types activate the HPA axis, albeit through different pathways. The hypothalamic-pituitary-adrenal (HPA or HTPA) axis is a complex set of direct influences and steroid-producing feedback interactions among the hypothalamus, the pituitary gland, and the adrenal glands. All vertebrates have an HPA, but the steroid-producing stress response is so important that even invertebrates and monocellular organisms have analogous systems.

The HPA is important to psychology because it is intimately involved with many mood disorders involving stress, including anxiety disorder, bipolar disorder, insomnia, PTSD, borderline personality disorder, ADHD, depression, and many others. Antidepressants work by reglulating the HPA axis.

The Function of the HPA Axis

The hypothalamus contains neurons that synthesize and secrete vasopressin and corticotropin-releasing hormone (CRH). These two hormones travel through blood to the anterior pituitary, where they cause the secretion of stored adrenocorticotropic hormone (ACTH). The ACTH acts on the adrenal cortex, which produces steroids—in humans, primarily the steroid cortisol. This causes a negative feedback cycle in which the steroids inhibit the hypothalamus and the pituitary gland, and it also causes the adrenal gland to produce the hormones epinephrine (also known as adrenaline) and norepinephrine.

Cortisol, Stress, and Health

In the process described above, the HPA axis ultimately produces cortisol. Studies on people show that the HPA axis is activated in different ways during chronic stress—depending on the type of stressor, the person's response to the stressor, and other factors. Stressors that are uncontrollable, threaten physical integrity, or involve trauma tend to have a high, flat profile of cortisol release (with lower-than-normal levels of cortisol in the morning and higher-than-normal levels in the evening) resulting in a high overall level of daily cortisol release. On the other hand, controllable stressors tend to produce higher-than-normal morning cortisol. Stress hormone release tends to decline gradually after a stressor occurs. In post-traumatic stress disorder there appears to be lower-than-normal cortisol release, and it is thought that a blunted hormonal response to stress may predispose a person to develop PTSD.

There is growing evidence that prenatal stress can affect HPA regulation in humans. Children who were stressed prenatally may show altered cortisol rhythms. For example, several studies have found an association between maternal depression during pregnancy and childhood cortisol levels. Prenatal stress has also been implicated in a tendency toward depression and short attention span in childhood. However, there is no clear indication that HPA disregulation caused by prenatal stress can alter adult behavior.