Depression: Major Depression & Unipolar Varieties

Biology of Depression - Neuroplasticity and Endocrinology

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

Neuroplasticity

The brain has a marvelous ability to sense and to respond to its environment. "Neuroplasticity" refers to our brain's flexible ability to grow and assume new shapes, and thereby enable memory and learning. For example, neurons can adjust their responsiveness, literally growing new synapses and strengthening existing synapses, 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 neurotransmitter activities. Specific receptors help neurons sense the environment and turn the genes which cause production of neurotransmitters and 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 synapses are received more slowly or with less sensitivity. If the receptors that have been downgraded or upgraded are also involved in regulating mood, then receptor up and downgrading will have an effect on mood.

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. This view has turned out to be inaccurate, however. We now know that we are constantly throughout our lives generating new neurons and neuronal 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. In contrast, chronic 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. Ongoing research continues to work towards finding definite causes for depression, developing diagnostic tests, and better treatments based on these key brain systems.

Endocrinology

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 by way of the bloodstream. Receiving organs in the body interpret hormonal signals (just as receiving neurons in the brain interpret neurotransmitter signals) and respond to their messages.

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

The term Circadian Rhythm refers to the 24-hour cycle of the body, which is determined by the amount of light that the hypothalamus senses in a day-night cycle. Both brain wave activity and hormone production are coupled to this cycle, and when the circadian rhythm is disturbed, mood disturbances can also result. Similar to circadian rhythms, seasonal rhythms are determined by the amount of daylight within a given season, and can also impact mood. As mentioned previously, individuals with Seasonal Affective Disorder (SAD) begin to feel increasingly depressed as the amount of light disappears in the winter. In contrast, these individuals experience a lift in mood as springtime (and more light) approaches. During other times of the year, people with SAD experience "normal" mental health.

The hypothalamus is also responsible for releasing stress hormones. When the brain assesses a potential threat, it produces a variety of hormones that help a person react to the situation. Many studies show that depressed individuals 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. As mentioned previously, depression is frequently associated with low levels of thyroid hormone (or hypothyroidism), and mood elevation is often associated with high levels of thyroid hormone (or hyperthyroidism). Treating hypothyroidism by supplementing or replacing thyroid hormone in the form of Synthroid 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, and may possibly be one of the reasons that men of this age become more prone to depression. 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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