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The Biology of Depression

The Biology of Depression

When you’re depressed, everyone around you has advice: “Snap out of it!” “Cheer up!” “It’s not that bad!” But, no matter how badly you would like to, you just can’t shake it off; it just gets worse. Depression is not just weakness, a character flaw or laziness. It is a serious medical condition with a strong biological component, similar to heart disease or diabetes. Although we still have pieces of the depression puzzle to solve, read on to learn what we know about the biology of depression.

The Brain

Depression, like all psychological disorder, is primarily based in the brain.

  • Brain Structures: The limbic system is the emotion and motivation centers of the brain. Depression is associated with a sad, apathetic or irritable mood, crying and a lack of motivation. It consists of a number of parts, including the hypothalamus, which controls the hormonal system in the body such as the pituitary gland and gonads (sex glands). The hypothalamus is the gland usually associated with our “survival behaviors”: hunger, thirst, sleep cycle and sexual arousal. Depression often decreases the sex drive and increases or decreases appetite. Other areas of the limbic system play a role in memory, attention, decision-making and pleasure, all areas that are impacted by depression.
  • Neurons: The individual cells of the brain use neurotransmitters—the chemical messengers of the brain—to communicate with each other. When a person is depressed, there is an imbalance in these chemicals, which can be corrected with the right medication. Neurotransmitters important in depression are serotonin, norepinephrine and dopamine.
    • Serotonin is associated with hunger, sleep, arousal and pain regulation. It helps us feel balanced, content and satisfied. This is believed to be the main neurotransmitter involved in depression.
    • Norepinephrine is usually associated with activity, vigilance or attentiveness. Symptoms of depression related to norepinephrine might include fatigue, loss of interest in activities and indifference in personal relationships.
    • Dopamine is part of our natural reward system, and is important in movement, attention, learning and addictions. Some symptoms of depression may be related to decreased dopamine levels, or problems with dopamine receptors.

Between neurons is a microscopic gap—called the Synaptic Cleft. Electrical impulses tell the neuron when it’s time to release neurotransmitters into the synaptic cleft so that it can send a message to the neuron next to it. Molecules of the neurotransmitter attach to receptor sites on the second neuron. Sometimes the message stops there, and sometimes it activates an electrical impulse that travels through the second neuron, and so on. The goal of most antidepressant medications is to increase the level of serotonin in your brain.


Depression tends to run in families. Although there are good arguments for the role of environment in depression, research (including studies of twins separated at birth) indicates that for some people, their genes put them at higher risk for developing depression. Recent studies suggest that a specific gene may be responsible for some cases of treatment-resistant depression. Although we cannot change our genetic make-up, medications and psychotherapy can help us change their impact on us.


Hormones help maintain balance for various functions in our body, such as the amount of sugar in our blood, our sleep cycles and sexual activity. Sex hormones also control the menstrual cycle in women, along with sexual interest and behavior in both sexes. They also play an important role in premenstrual dysphoric disorder, or PMDD, a clinical condition in which women experience increased anxiety, sudden mood shifts, intense sadness or irritability in the second half of the menstrual cycle and during the first days of menses. PMDD is more than just typical PMS. It involves a significant change in mood and functioning from the rest of the month. Although PMDD is linked to the menstrual cycle and sex hormones, some researchers believe that neurotransmitters are also involved. PMDD is typically treated with antidepressant medications.

Another hormone that can be important in depression is melatonin, which is secreted by the pineal gland at night, and helps regulate our sleep cycles and seasonal rhythms. Insomnia (not sleeping enough) and hypersomnia (sleeping too much) are common symptoms of anxiety and depression.

Stress is also important in depression and anxiety. When we are stressed our bodies produce hormones that help us prepare to fight or flee. One stress hormone is cortisol. Prolonged exposure to high cortisol levels affects all of our body systems, including our immune system. This can increase the likelihood of getting sick or make it more difficult to recover from illnesses. Learning to better deal with stress in everyday life may help alleviate some of the symptoms of depression and anxiety such as restlessness, fatigue and insomnia.