Why Zebras Don't Get Ulcers: A Guide to Stress, Stress Related Diseases, and Coping

Major depression, a leading cause of disability, is relatively common. It is more severe and longer-lasting than milder depressed moods, and it has genetic and environmental causes.

The “defining feature” of major depression is anhedonia or dysphoria, or the lack of pleasure, and it is often accompanied by guilt, grief, and delusional thinking. Some people with major depression may also experience psychomotor retardation, which occurs when physical movements and speaking take significant concentration and effort. Although many judge people with major depression as self-indulgent, the condition is a medical disease with measurable symptoms, like sleep disruption, high glucocorticoid levels, and memory issues. Depressions come in multiple types, such as unipolar, bipolar or manic depression, and seasonal affective disorder. Bouts of depression are often cyclical.

Neurons are separated by gaps called synapses, and neurons use neurotransmitters to send signals between synapses from the axons of one cell to the dendrites of an adjacent neuron. Afterward, neurotransmitters are released from the dendrites and either reabsorbed by axons or flushed out. However, these systems can misfunction. Research suggests that neurotransmitter dysfunction causes depression, supported by the fact that anti-depressant medications, which work to strengthen the neurotransmitter signals, provide relief from depressive symptoms.

However, researchers have not been able to make any definitive conclusions, as they are unsure what specific neurotransmitter—dopamine, serotonin, or norepinephrine—is the issue, and the timing of drug administration and symptom relief and the unpredictability of anti-depressant effectiveness suggest the underlying process is more complicated than simply not having enough of a certain neurotransmitter. Sapolsky suggests that different forms of depression have different underlying factors, but there is not much data available on the topic.

The cortex manages cognition, the limbic system processes emotions, and the other areas of the brain contribute to involuntary biological processes, such as blood pressure and hormone management. A simplified view of depression is that the cortex convinces other areas of the brain that its negative thoughts are as critical as an acute physical stressor. When a certain area of the cortex—the anterior cingulate cortex (ACC), which is involved with negative emotions—is separated from the rest of the brain, depression ceases. The ACC and the amygdala are hyperactive in individuals with depression.

The prefrontal cortex (PFC) deals with emotions, but the processes are divided, with the left half of the PFC activated during positive emotions and the right activated for negative emotions. People with depression show increased activity in the right half of the PFC. Diseases that cause overactivity in the immune system are correlated with higher rates of depression, and cytokines, a messenger cell that is sometimes used in cancer treatment, can cause depression. Hormones and depression impact one another: Females are more at-risk for unipolar depression, which, Sapolsky suggests, may be due to fluctuating ratios of estrogen and progesterone.

Experiencing a significant stressor increases one’s risk of developing major depression, and multiple stress-depression events trigger a cyclical response—“somewhere around the fourth depression or so, a mad clockwork takes over, and the depressive waves crash, regardless of whether the outside world pummels you with stressors” (292). High glucocorticoid levels are associated with depression and can trigger genetic components of depression. Vice versa, depression causes elevated glucocorticoid levels.

Glucocorticoids may contribute to the neurotransmitter abnormalities thought to underlie depression, and they may explain why people with depression are more likely to experience immunosuppression, osteoporosis, heart disease, memory impairment, and hippocampal and frontal cortex atrophy. Researchers are exploring whether some cases of depression can be treated with glucocorticoid suppressants, but the treatment may not be effective for everyone, and it may have adverse side effects.

Sapolsky discusses Freud’s take on depression, which Freud had attributed to ambivalence following the loss of a loved one. After the loss of a loved one, people with major depression tend to take on personality traits—particularly irritating traits—of the person they lost. Freud’s perspective supports the idea that major depression is internalized aggression. Learned helplessness is another trait of stress and depression. Stressed rats struggle to learn how to perform simple tasks that may help relieve their stress, and they develop dysphoria, sleep issues, and sometimes engage in self-harm. Learned helplessness has also been demonstrated in human studies.

Sapolsky reiterates that there are multiple explanations for depression, and he suggests that stress is the “unifying theme” running throughout the hypothesized causes of the disease. Most people are able to recover from stressors, but those with depression have a biological vulnerability that obstructs the recovery process. There is a gene that impacts 5-HTT, a serotonin transporter that causes serotonin reuptake from synapses. The gene determines how effectively serotonin is removed, and glucocorticoids impact the quantity of 5-HTT. From this emerges a simple model of depression: A stressor occurs, resulting in symptoms of depression and, depending on a person’s gene variant, the person may recover quickly from the stressor or may experience a major depression.

Stress-related psychological differences are exemplified through two male baboons, Gary and Kenneth. Gary, who has high glucocorticoids and poor mental and physical health, is aggressively competitive and has been successful in achieving a high rank and multiple sexual partners. Kenneth, also high-ranking, prioritizes relationships and elected not to assume the top-ranking position: He is happy and healthy with low glucocorticoid levels. Like modern humans, these baboons have ample resources, so their stress is predominantly psychological.

Sapolsky and his associates documented behaviors in relation to glucocorticoid levels. Male baboons with low glucocorticoids are adept at distinguishing between threatening and non-threatening social situations and whether they won or lost a dispute, are more assertive during tense social situations, are more likely to displace their aggression by attacking lower-ranked members and are more likely to have platonic relationships with females.

Suomi, who conducted similar studies on macaques, found a correlation between the personalities of young monkeys and their fathers, even when the father was not present, suggesting a genetic component to personality. However, personality aspects can be countered through the mother’s nurturing behavior, showing a strong environmental component. Stress-related issues in primates can develop from a mismatch between the level of stressors and the subsequent stress-responses and from not taking advantage of coping strategies. Studies in humans show a correlation between personality types and vulnerability to stress-related diseases; however, people should be skeptical of the connections. For instance, blaming otherwise unexplained repeated miscarriages on a woman’s personality is damaging, and it is more likely that the underlying causes haven’t been discovered.

Anxiety disorders are characterized by persistent vigilance and insecurity. Anxiety includes the subtypes of post-traumatic stress disorder, generalized anxiety disorder, obsessive-compulsive disorder, and specific phobias. People with anxiety perceive that stressors are everywhere and that their safety depends on maintaining constant coping mechanisms. Anxiety is associated with increased levels of catecholamines—epinephrine and norepinephrine—rather than with high glucocorticoids. Some sources of anxiety, such as having one’s breathing obstructed, are innate, but most sources of anxiety are implicitly learned. This implicit learning is regulated by the amygdala, which is hyperreactive in people with anxiety.

Stress decreases the size and function of the hippocampus, and it strengthens the connections and functions of the amygdala. One expert, Joseph LeDoux, proposed that severe stress inhibits the hippocampus and activates the amygdala so that traumatic memories are not properly consolidated. Thus, the traumatic memory is mediated by the amygdala rather than the hippocampus.

Researchers have found a link between Type-A personalities and cardiovascular disease. Type-A personalities are characterized by competitiveness, impatience, and hostility. Insecurity-driven hostility is the primary trait associated with increased rates of death and disease. When Type-A individuals learn to manage their hostility, their health risks drop. Type-A behaviors were first documented by Dr. Meyer Friedman, a cardiologist who was frustrated when he had to repeatedly reupholster the chairs in his waiting room. The upholsterer noted that the wear patterns along the front edge of the seat and arm rests were unusual, but Friedman did not take note of the comment until years later.

People with repressive personalities claim not to experience a significant amount of stress, but their stress-responses are chronically activated. People with repressive personalities are stoic, inflexible, follow a strict routine, and have black-and-white thinking. They are driven by a strong need for conformity and fears of social condemnation. They have high glucocorticoid levels and are vulnerable to cardiac issues, which, Sapolsky suggests, develop from the individual’s attempts to construct a world without stress.