It’s often said that depression results from a chemical imbalance, but that figure of speech doesn’t capture how complex the disease is. Research suggests that depression doesn’t spring from simply having too much or too little of certain brain chemicals. Rather, there are many possible causes of depression, including faulty mood regulation by the brain, genetic vulnerability, stressful life events, medications, and medical problems. It’s believed that several of these forces interact to bring on depression.
To be sure, chemicals are involved in this process, but it is not a simple matter of one chemical being too low and another too high. Rather, many chemicals are involved, working both inside and outside nerve cells. There are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.
With this level of complexity, you can see how two people might have similar symptoms of depression, but the problem on the inside, and therefore what treatments will work best, may be entirely different.
Researchers have learned much about the biology of depression. They’ve identified genes that make individuals more vulnerable to low moods and influence how an individual responds to drug therapy. One day, these discoveries should lead to better, more individualized treatment (see “From the lab to your medicine cabinet”), but that is likely to be years away. And while researchers know more now than ever before about how the brain regulates mood, their understanding of the biology of depression is far from complete.
What follows is an overview of the current understanding of the major factors believed to play a role in depression.
The brain’s impact on depression
Popular lore has it that emotions reside in the heart. Science, though, tracks the seat of your emotions to the brain. Certain areas of the brain help regulate mood. Researchers believe that — more important than levels of specific brain chemicals — nerve cell connections, nerve cell growth, and the functioning of nerve circuits have a major impact on depression. Still, their understanding of the neurological underpinnings of mood is incomplete.
Regions that affect mood
Increasingly sophisticated forms of brain imaging — such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) — permit a much closer look at the working brain than was possible in the past. An fMRI scan, for example, can track changes that take place when a region of the brain responds during various tasks. A PET or SPECT scan can map the brain by measuring the distribution and density of neurotransmitter receptors in certain areas.
Use of this technology has led to a better understanding of which brain regions regulate mood and how other functions, such as memory, may be affected by depression. Areas that play a significant role in depression are the amygdala, the thalamus, and the hippocampus (see Figure 1).
Research shows that the hippocampus is smaller in some depressed people. For example, in one fMRI study published in The Journal of Neuroscience, investigators studied 24 women who had a history of depression. On average, the hippocampus was 9% to 13% smaller in depressed women compared with those who were not depressed. The more bouts of depression a woman had, the smaller the hippocampus. Stress, which plays a role in depression, may be a key factor here, since experts believe stress can suppress the production of new neurons (nerve cells) in the hippocampus.
Researchers are exploring possible links between sluggish production of new neurons in the hippocampus and low moods. An interesting fact about antidepressants supports this theory. These medications immediately boost the concentration of chemical messengers in the brain (neurotransmitters). Yet people typically don’t begin to feel better for several weeks or longer. Experts have long wondered why, if depression were primarily the result of low levels of neurotransmitters, people don’t feel better as soon as levels of neurotransmitters increase.
The answer may be that mood only improves as nerves grow and form new connections, a process that takes weeks. In fact, animal studies have shown that antidepressants do spur the growth and enhanced branching of nerve cells in the hippocampus. So, the theory holds, the real value of these medications may be in generating new neurons (a process called neurogenesis), strengthening nerve cell connections, and improving the exchange of information between nerve circuits. If that’s the case, medications could be developed that specifically promote neurogenesis, with the hope that patients would see quicker results than with current treatments.
Figure 1: Areas of the brain affected by depression
Amygdala: The amygdala is part of the limbic system, a group of structures deep in the brain that’s associated with emotions such as anger, pleasure, sorrow, fear, and sexual arousal. The amygdala is activated when a person recalls emotionally charged memories, such as a frightening situation. Activity in the amygdala is higher when a person is sad or clinically depressed. This increased activity continues even after recovery from depression.
Thalamus: The thalamus receives most sensory information and relays it to the appropriate part of the cerebral cortex, which directs high-level functions such as speech, behavioral reactions, movement, thinking, and learning. Some research suggests that bipolar disorder may result from problems in the thalamus, which helps link sensory input to pleasant and unpleasant feelings.
Hippocampus: The hippocampus is part of the limbic system and has a central role in processing long-term memory and recollection. Interplay between the hippocampus and the amygdala might account for the adage “once bitten, twice shy.” It is this part of the brain that registers fear when you are confronted by a barking, aggressive dog, and the memory of such an experience may make you wary of dogs you come across later in life. The hippocampus is smaller in some depressed people, and research suggests that ongoing exposure to stress hormone impairs the growth of nerve cells in this part of the brain.
Nerve cell communication
The ultimate goal in treating the biology of depression is to improve the brain’s ability to regulate mood. We now know that neurotransmitters are not the only important part of the machinery. But let’s not diminish their importance either. They are deeply involved in how nerve cells communicate with one another. And they are a component of brain function that we can often influence to good ends.
Neurotransmitters are chemicals that relay messages from neuron to neuron. An antidepressant medication tends to increase the concentration of these substances in the spaces between neurons (the synapses). In many cases, this shift appears to give the system enough of a nudge so that the brain can do its job better.
Bible verses for today’s meditation and inspiration: Matthew E. McLaren
Rejoice always, pray continually, give thanks in all circumstances; for this is God’s will for you in Christ Jesus. 1 Thessalonians 5:16-18 NIV
The Lord your God is with you, the Mighty Warrior who saves. He will take great delight in you; in his love he will no longer rebuke you, but will rejoice over you with singing. Zephaniah 3:17 NIV
Rejoice in the Lord always. I will say it again: Rejoice! Philippians 4:4 NIV
Be joyful in hope, patient in affliction, faithful in prayer. Romans 12:12 NIV
When anxiety was great within me, your consolation brought me joy. Psalm 94:19 NIV
The Lord has done it this very day; let us rejoice today and be glad. Psalm 118:24 NIV
Though the fig tree does not bud and there are no grapes on the vines, though the olive crop fails and the fields produce no food, though there are no sheep in the pen and no cattle in the stalls, yet I will rejoice in the Lord, I will be joyful in God my Savior. Habakkuk 3:17-18 NIV
You make known to me the path of life; you will fill me with joy in your presence, with eternal pleasures at your right hand. Psalm 16:11 NIV
Though you have not seen him, you love him; and even though you do not see him now, you believe in him and are filled with an inexpressible and glorious joy, for you are receiving the end result of your faith, the salvation of your souls. 1 Peter 1:8-9 NIV
I delight greatly in the Lord; my soul rejoices in my God. For he has clothed me with garments of salvation and arrayed me in a robe of his righteousness, as a bridegroom adorns his head like a priest, and as a bride adorns herself with her jewels. Isaiah 61:10 NIV
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