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Biology of Depression - Neurotransmitters

Rashmi Nemade, Ph.D., Natalie Staats Reiss, Ph.D., and Mark Dombeck, Ph.D.

A literal ton of research has been done on the causes of depression. Below is a brief discussion of the multiple biological, psychological and social factors that have been identified as being related to the development of depression. In context of the Diathesis-Stress hypothesis, the biological factors typically function as diatheses, the psychological factors may serve as diatheses or stressors, and sociological factors tend to function as stressors or triggers.

Biology of Depression

You may have heard that depression is the result of a simple imbalance of brain chemicals. Although brain chemicals are certainly part of the cause, this explanation is too simplistic. Even just considering the biological dimension of depression, the brain has multiple layers of complexity.

Neurochemistry

Neurotransmitters

The brain uses a number of chemicals as messengers to communicate with other parts of itself and with the nervous system. These chemical messengers, called neurotransmitters, are released and received by the brain's many nerve cells, which are also called neurons. Neurons are constantly communicating with each other by way of exchanging neurotransmitters. This communication system is essential to all of the brain's functions.

A tiny space called a synapse connects neurons to one another. In a simple scenario, one neuron (the sender) sends a neurotransmitter message across the synapse and the next neuron (the receiver) receives that message by way of a receptor embedded on its surface. Receptors are tiny molecules that function like a lock on a door. Receptors have chemical channels with particular shapes, which perfectly match the shape of neurotransmitter molecules that are sent across the synapse. When a "matching" neurotransmitter and receptor come into contact with each other, the neurotransmitter fits itself into the receptor molecule's channel. As a result, the receptor becomes activated or opened, just like when a key enters a lock and turns to open it. When there are no neurotransmitter molecules around to unlock the receptors, the receptors remain in a closed or inactive state.

In music, it's not just the notes that make up a melody; it is also the spaces or rests between the notes that make each note stand out and be distinct. It's exactly the same with regard to neurotransmitters and synapses. There needs to be some quiet time between neurotransmitter messages for those messages to have any meaning. It is important that receptors be allowed to reset and deactivate between messages so that they can become ready to receive the next burst of neurotransmitters. In order to achieve this "resetting", the receptors relax and release their captured neurotransmitters back into the synapse where about 90% of them get taken up again (in a process called reuptake) by the original sending neuron. The neurotransmitters are then repackaged and reused the next time a message needs to be sent across the synapse. Even though this seems like a complicated set of steps, this entire information transmission cycle occurs in the brain within in a matter of seconds. Any problem that interrupts the smooth functioning of this chain of chemical events can negatively impact both the brain and nervous system.

Depression has been linked to problems or imbalances in the brain with regard to the neurotransmitters serotonin, norepinephrine, and dopamine. The evidence is somewhat indirect on these points because it is very difficult to actually measure the level of neurotransmitter in a person's brain. What we do know is that antidepressant medications (used to treat the symptoms of depression) are known to act upon these particular neurotransmitters and their receptors. We'll talk more about antidepressant medications in the treatment section of this article.

The neurotransmitter serotonin is involved in regulating many important physiological (body-oriented) functions, including sleep, aggression, eating, sexual behavior, and mood. Serotonin is produced by serotonergic neurons. Current research suggests that a decrease in the production of serotonin by these neurons can cause depression in some people, and more specifically, a mood state that can cause some people to feel suicidal.

In the 1960s, the "catecholamine hypothesis" was a popular explanation for why people developed depression. This hypothesis suggested that a deficiency of the neurotransmitter norepinephrine (also known as noradrenaline) in certain areas of the brain was responsible for creating depressed mood. More recent research suggests that there is indeed a subset of depressed people who have low levels of norepinephrine. For example, autopsy studies show that people who have experienced multiple depressive episodes have fewer norepinephrinergic neurons than people who have no depressive history. However, research results also tell us that not all people experience mood changes in response to decreased norepinephrine levels. Some people who are depressed actually show hyperactivity within the neurons that produce norepinephrine. More current studies suggest that in some people, low levels of serotonin trigger a drop in norepinephrine levels, which then leads to depression.

Another line of research has investigated linkages between stress, depression, and norepinephrine. Norepinephrine helps our bodies to recognize and respond to stressful situations. Researchers suggest that people who are vulnerable to depression may have a norepinephrinergic system that doesn't handle the effects of stress very efficiently.

The neurotransmitter dopamine is also linked to depression. Dopamine plays an important role in regulating our drive to seek out rewards, as well as our ability to obtain a sense of pleasure. Low dopamine levels may in part explain why depressed people don't derive the same sense of pleasure out of activities or people that they did before becoming depressed.

Recently, another neurotransmitter, glutamate, has been implicated in depression as well, but more research is necessary at this time to determine the nature of this relationship.