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Biology of Depression - Neuroplasticity and Endocrinology

Randi Fredricks, Ph.D., edited by Kathryn Patricelli, MA


Our brains are continually remodeling themselves throughout our lifetimes based on experiences, behavior, genes, etc. The brain has a marvelous ability to sense and to respond to its environment. "Neuroplasticity" refers to our brain's ability to reorganize itself by forming new neural connections throughout life.† These connections allow memory and learning to happen. For example, neurons can adjust their responsiveness, literally growing new synapses (spaces between neurons) and strengthening existing ones.† This happens depending on the sorts of stimulation they receive. In addition, neurons can be "reprogrammed" in response to various situations. For example, axons (extensions of neuron cell bodies that project from one location to another) from one area of the brain can be rerouted to enable functioning in a damaged part of the brain after a stroke has occurred.

An important aspect of neuroplasticity involves the monitoring of the activities of neurotransmitter. Specific receptors help neurons sense the environment and turn on the genes.† This causes production of neurotransmitters and turns their receptors on or off. For example, if an individual has just experienced a stressful situation, the brain senses the rise in stress level and may turn off or turn down the genes that make neurotransmitter receptors. When fewer receptors are available, messages sent across spaces are received more slowly or with less sensitivity. If the receptors that have been downgraded or upgraded are also involved in controlling mood, then this will have an effect on mood. Exercise and physical activity in general have a major effect on neurotransmitters that stimulate the growth and recovery of brain cells.† This is why exercise has been connected with relieving depression.

Until recently, it was thought the brain did not make new neurons to replace ones that were destroyed, and that the adult brain had all of the neurons it would ever produce. We now know that we are constantly throughout our lives generating new neurons and pathways within certain areas of the brain involved in memory and emotion. In addition, research suggests that antidepressant medications and electroconvulsive therapy (ECT) seem to increase the growth of new neurons in these key brain areas.† However, long-term stress seems to decrease cell growth in these areas. Based on this evidence, we can conclude that a decreased number of neurons in the emotional centers of the brain can lead to slower reactivity and depressive symptoms.

The neurotransmitter traffic and neuroplastic activity in the brain and nervous system is constant and complicated. Research continues to work towards finding definite causes for depression, developing diagnostic tests, and better treatments based on these key brain systems.


Neurotransmitters are not the only important chemical messengers in the body. The body also uses hormones as chemical messengers. Produced in the endocrine system, hormones circulate from one organ to another through the bloodstream. Receiving organs in the body interpret hormonal signals and respond to their messages.

The endocrine and nervous systems are linked by the hypothalamus.† This is a centrally located 'switching station' within the brain. The hypothalamus is an exceptionally complex brain region. It controls many different body functions such as blood pressure, appetite, immune responses, body temperature, maternal behavior, and body rhythms dealing with circadian and seasonal rhythms.

The term circadian rhythm refers to the approximately 24-hour cycle of the body.† This cycle is determined by the amount of light that the hypothalamus in the brain senses in a day-night cycle. Both brain wave activity and hormone production are coupled to this cycle.† When the circadian rhythm is disturbed, mood disturbances can also happen. Similar to circadian rhythms, seasonal rhythms are determined by the amount of daylight within a given season.† This can also impact mood. Individuals with major depressive disorder with a seasonal pattern begin to feel increasingly depressed as the amount of light disappears in the winter. Then these individuals experience a lift in mood as springtime (and more light) approaches. During other times of the year, people with this seasonal pattern experience "normal" mental health.

The hypothalamus is also responsible for releasing stress hormones. When the brain identifies a potential threat, it produces a variety of hormones that help a person react to the situation. Many studies show that people with depression have increased levels of stress hormones. In addition to the hypothalamus, other endocrine organs such as the thyroid, adrenal glands, the ovaries and testes have been linked to depression. The thyroid gland, which is located in the neck, produces thyroid hormone. Depression is frequently associated with low levels of thyroid hormone (known as hypothyroidism).† Mood elevation is often associated with high levels of thyroid hormone (known as hyperthyroidism). Treating hypothyroidism by supplementing or replacing thyroid hormone may sometimes alleviate depression.

The adrenal glands, located near the kidneys, produce hormones that are involved in metabolism, immune function, and the stress response. The main hormone of the adrenal glands, cortisol, is higher in depressed individuals. The ovaries, which produce estrogen, are thought to be one of the main reasons why women run a higher risk of developing depression than men. Decreased levels of estrogen can alter the activity of neurotransmitters such as serotonin and norepinephrine, which can then lead to depression. At times in women's lives when estrogen levels are lower than usual, such as during the premenstrual phase, following the birth of a baby (postpartum period), or around the time of menopause, an increased tendency or vulnerability towards depression is common.

Testosterone, a hormone produced by the testes in males, may also be linked to depression. A decrease in testosterone after the age of 50 is well documented.† This may possibly be one of the reasons that men of this age are more likely to be depressed. Unlike the link between decreasing estrogen and depression, the relationship between testosterone and depression is not as clear. Researchers are still trying to determine if there is a reliable link between testosterone and depressive symptoms.

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