How genes and life events affect mood and depression

Family history and stress play major roles in depression

Every part of your body, including your brain, is controlled by genes. Genes make proteins that are involved in biological processes. Throughout life, different genes turn on and off, so that — in the best case — they make the right proteins at the right time. But if the genes get it wrong, they can alter your biology in a way that results in your mood becoming unstable. In a person who is genetically vulnerable to depression, any stress (a missed deadline at work or a medical illness, for example) can then push this system off balance.

Mood is affected by dozens of genes, and as our genetic endowments differ, so do our depressions. The hope is that as researchers pinpoint the genes involved in mood disorders and better understand their functions, depression treatment can become more individualized and more successful. Patients would receive the best medication for their type of depression.

Another goal of gene research, of course, is to understand how, exactly, biology makes certain people vulnerable to depression. For example, several genes influence the stress response, leaving us more or less likely to become depressed in response to trouble.

Perhaps the easiest way to grasp the power of genetics is to look at families. It is well known that depression and bipolar disorder run in families. The strongest evidence for this comes from the research on bipolar disorder. Half of those with bipolar disorder have a relative with a similar pattern of mood fluctuations. Studies of identical twins, who share a genetic blueprint, show that if one twin has bipolar disorder, the other has a 60% to 80% chance of developing it, too. These numbers don't apply to fraternal twins, who — like other biological siblings — share only about half of their genes. If one fraternal twin has bipolar disorder, the other has a 20% chance of developing it.

The evidence for other types of depression is more subtle, but it is real. A person who has a first-degree relative who suffered major depression has an increase in risk for the condition of 1.5% to 3% over normal.

One important goal of genetics research — and this is true throughout medicine — is to learn the specific function of each gene. This kind of information will help us figure out how the interaction of biology and environment leads to depression in some people but not others.

Stressful life events

At some point, nearly everyone encounters stressful life events: the death of a loved one, the loss of a job, an illness, or a relationship spiraling downward. Some must cope with the early loss of a parent, violence, or sexual abuse. While not everyone who faces these stresses develops a mood disorder — in fact, most do not — stress plays an important role in depression.

As the previous section explained, your genetic makeup influences how sensitive you are to stressful life events. When genetics, biology, and stressful life situations come together, depression can result.

Stress has its own physiological consequences. It triggers a chain of chemical reactions and responses in the body. If the stress is short-lived, the body usually returns to normal. But when stress is chronic or the system gets stuck in overdrive, changes in the body and brain can be long-lasting.

Temperament shapes behavior

Genetics provides one perspective on how resilient you are in the face of difficult life events. But you don’t need to be a geneticist to understand yourself. Another way to look at resilience is by understanding your temperament. Temperament—for example, how excitable you are or whether you tend to withdraw from or engage in social situations—is determined by your genetic inheritance and by the experiences you’ve had during your life. Some people are able to make better choices in life once they appreciate their habitual reactions to people and to life events.

Cognitive psychologists point out that your view of the world and, in particular, your unacknowledged assumptions about how the world works also influence how you feel. You develop your viewpoint early on and learn to automatically fall back on it when loss, disappointment, or rejection occurs. For example, you may come to see yourself as unworthy of love, so you avoid getting involved with people rather than risk losing a relationship. Or you may be so self-critical that you can’t bear the slightest criticism from others, which can slow or block your career progress.

Yet while temperament or worldview may have a hand in depression, neither is unchangeable. Therapy and medications can shift thoughts and attitudes that have developed over time.

The article also highlights several other interesting observations. For instance, the gene variants in question are also found in other mammals, which suggests the variants may have important roles in helping people adapt or survive. This may explain why depression persists in the human gene pool. In addition, a person’s genes may affect brain development over time, including how the brain adapts to various environmental influences. The variants identified in the study are not specific to depression but are also correlated with other mental disorders, such as schizophrenia. The gene variants also overlap with genes involved in obesity and sleep quality. Finally, the authors said that the findings confirm the targets of known antidepressant medications and may offer clues for developing new drugs to treat depression.

How stress affects the body

Stress can be defined as an automatic physical response to any stimulus that requires you to adjust to change. Every real or perceived threat to your body triggers a cascade of stress hormones that produces physiological changes. We all know the sensations: your heart pounds, muscles tense, breathing quickens, and beads of sweat appear. This is known as the stress response.

The stress response starts with a signal from the part of your brain known as the hypothalamus. The hypothalamus joins the pituitary gland and the adrenal glands to form a trio known as the hypothalamic-pituitary-adrenal (HPA) axis, which governs a multitude of hormonal activities in the body and may play a role in depression as well.

When a physical or emotional threat looms, the hypothalamus secretes corticotropin-releasing hormone (CRH), which has the job of rousing your body. Hormones are complex chemicals that carry messages to organs or groups of cells throughout the body and trigger certain responses. CRH follows a pathway to your pituitary gland, where it stimulates the secretion of adrenocorticotropic hormone (ACTH), which pulses into your bloodstream. When ACTH reaches your adrenal glands, it prompts the release of cortisol.

The boost in cortisol readies your body to fight or flee. Your heart beats faster — up to five times as quickly as normal — and your blood pressure rises. Your breath quickens as your body takes in extra oxygen. Sharpened senses, such as sight and hearing, make you more alert.

CRH also affects the cerebral cortex, part of the amygdala, and the brainstem. It is thought to play a major role in coordinating your thoughts and behaviors, emotional reactions, and involuntary responses. Working along a variety of neural pathways, it influences the concentration of neurotransmitters throughout the brain. Disturbances in hormonal systems, therefore, may well affect neurotransmitters, and vice versa.

Normally, a feedback loop allows the body to turn off "fight-or-flight" defenses when the threat passes. In some cases, though, the floodgates never close properly, and cortisol levels rise too often or simply stay high. This can contribute to problems such as high blood pressure, immune suppression, asthma, and possibly depression.

Studies have shown that people who are depressed or have dysthymia typically have increased levels of CRH. Antidepressants and electroconvulsive therapy are both known to reduce these high CRH levels. As CRH levels return to normal, depressive symptoms recede. Research also suggests that trauma during childhood can negatively affect the functioning of CRH and the HPA axis throughout life.

Early losses and trauma

Certain events can have lasting physical, as well as emotional, consequences. Researchers have found that early losses and emotional trauma may leave individuals more vulnerable to depression later in life.

Profound early losses, such as the death of a parent or the withdrawal of a loved one's affection, may resonate throughout life, eventually expressing themselves as depression. When an individual is unaware of the wellspring of his or her illness, he or she can't easily move past the depression. Moreover, unless the person gains a conscious understanding of the source of the condition, later losses or disappointments may trigger its return.

Traumas may also be indelibly etched on the psyche. A small but intriguing study in the Journal of the American Medical Association showed that women who were abused physically or sexually as children had more extreme stress responses than women who had not been abused. The women had higher levels of the stress hormones ACTH and cortisol, and their hearts beat faster when they performed stressful tasks, such as working out mathematical equations or speaking in front of an audience.

Many researchers believe that early trauma causes subtle changes in brain function that account for symptoms of depression and anxiety. The key brain regions involved in the stress response may be altered at the chemical or cellular level. Changes might include fluctuations in the concentration of neurotransmitters or damage to nerve cells. However, further investigation is needed to clarify the relationship between the brain, psychological trauma, and depression.

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