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The Brain and Depression
By Sarah Faller
Introduction
Many people think that depression is a form of weakness. Something that is in our control;
something we can change about ourselves; something we can just “get over.” Unfortunately,
it’s not that simple. It would be nice if it was as easy as changing our perspective, but our brain
and our genes are more intricate than that. Around one in four people will be effected by a
mental disorder, depression being one of them. It’s crucial that people understand the basic
parts of the brain and depression to take care of the most important muscle in the body.
Anatomy of the Brain and Important Terms
The Cerebrum: The Cerebrum is the largest part of the brain. It is usually divided into two parts,
the left cerebral hemisphere and the right cerebral hemisphere. For the average human, the
right hemisphere controls the left side of the body and is responsible for rational and logical
thinking. The left hemisphere controls the right side of the brain and is involved with creative
thinking (Brain). The hemispheres are also divided into lobes. The frontal lobe is involved with
thinking and developing personality; temporal lobes are involved with forming memories and
processing sounds; parietal lobes are responsible for sensation and integrating different bits of
information; occipital lobes are the primary vision centers (Brain).
The Brain Stem: “The brainstem is like the hard-drive of a computer” (Brain). There are three
main parts to the brain stem; the midbrain, the pons, and the medulla oblongata. This part
controls vital functions of the body such as breathing, swallowing, hunger and cardiac function
by connecting the brain to other parts of the body to send messages back and forth.
The Cerebellum: The cerebellum contains more nerve cells than both hemispheres combined.
This part of the brain is primarily in control of fine motor skills, voluntary muscle movements,
and managing equilibrium (Brain).
The Limbic System: The limbic system, also referred to as the emotional brain, will be important
to support the understanding of mental disorders. This is where memory is stored and
emotions are created. These two functions combine together to assign behaviors with negative
or positive judgments (Looi). The limbic system consists of four parts, but for the purposes of
this paper the two important parts are the Amygdala and the Hippocampus. The Amygdala is
where emotions are produced and where fear is registered. It’s found to trigger responses in
the body such as an increase in heart rate, drop in temperature, stress hormone release etc.
The Hippocampus is responsible for forming memory and storing it into long term memory. This
is also the part of the brain that registers fear and interprets incoming nerve signals and spatial
relationships (Looi).
Neurons
Neurons are the basic working unit of the brain
and the nervous system; they specialize in
transmitting nerve impulses between the brain
and other parts of the body. A neuron is made
out of three basic parts, the axon, the dendrites,
and the cell body. The axon which sends
impulses and extends from the cell body to
deliver messages to another nerve cell. It can be as long as one inch to several feet. Dendrites
extend from the cell body and receives chemical and electrical impulses from other neurons.
The gap between dendrites and neighboring cells are called synapses. The Cell body is
comprised of the cytoplasm, cell organelles and the nucleus. The nucleolus contains DNA and
other information necessary for the neuron to function. The cytoplasm in the cell body fills the
cell with chemicals and organelles needed for the cell to operate (NIMH).
Neurotransmitters
Neurotransmitters are chemicals in the brain that communicate chemical signals between
neurons. There are two types of transmitters, inhibitory and excitatory. Inhibitory transmitters
calm the brain while the excitatory brains stimulate the brain. The ratio of these transmitters
are crucial to a healthy and balanced mind and body. However, it is easy to deplete inhibitory
transmitters which can lead to mental illnesses (What Are…). Three important
neurotransmitters that will later be referenced in this paper are, serotonin, dopamine, and
glutamate: Serotonin controls mood, appetite, and sleep. Dopamine controls movement and
sending information to the front of the brain and glutamate is most common excitatory
transmitter that controls a variety of functions throughout the brain and nervous system. When
released it increases the chances of a neuron firing.
The Brain and Depression
The general consensus is that chemical imbalances are the primary cause of depression,
specifically a lack of serotonin. However, new research suggests that the only supportive
evidence behind this was when a patient was prescribed serotonin, it helped alleviate some of
their symptoms; there was no empirical data explaining exactly why. Just because a drug may
ease symptoms does not mean the problem was caused by the chemical problem the drug
fixes. For example, Aspirin (Serotonin) reduces headaches, but headaches are not caused by a
lack of aspirin (Serotonin) (Arkowits). One of the main reasons this hypothesis has been
accepted uncritically is because of pharmaceutical company’s incentive to make money. A
challenge to this hypothesis is that many depressed patients are not cured by SSRIs
(Antidepressants). Michael Gitlin, professor from UCLA, reported that only one third of his
patients improved by the use of SSRI’s. There is also a newly developed antidepressant,
Stablon, which actually decreases levels of serotonin in synapses. When Stablon was given to
patients for experimental purposes, it was found that the results were unpredictable
(Arkowits). Some patients felt the same, some felt better, and others felt even more depressed.
In recent years’ scientists have found that brain cell growth, brain cell connections, functioning
nerve circuits, and genetic factors could have a greater role in the cause of depression (Harvard
Health).
In 2015 ENIGMA, BMR, and the University of Sydney conducted a study that examined the brain
of a depressed patient (University of Sydney). This study showed that the Hippocampus of a
depressed person was significantly smaller than that of an average person. The study also
showed that the longer a person fought depression, the smaller their hippocampus tended to
be; the cells and networks in the brain deteriorate. Sandrine Thuret, a neuroscientist, found
that some cancer patients develop symptoms of depression after they were told they were
cured. This is because the drugs they were given not only stopped cancer cells from multiplying,
but also stopped new neurons from being generated, causing the patients to get depressed
(Thuret). Subsequent studies have shown that neurogenesis, the creation of new neurons, in
this region causes the brain to return back to normal and mood to improve.
One contributing factor to the decreasing size of the hippocampus is the effect of stress on the
development of new neurons. The stress response begins when the hypothalamus sends a
signal to the body by secreting corticotrophin (CRH). The hormones carry messages to organs
and groups of cells in the body which trigger responses. One of the responses is the secretion of
adrenocorticotropic hormone (ACTH), which is then released into the bloodstream. Once the
ACTH reaches the adrenal glands, the adrenal gland releases cortisol, a steroid hormone, into
the bloodstream; this is known as the “fight or flee” hormone (Harvard Health). Although low
amounts of cortisol aren’t harmful, over long periods of time it can have negative effects on the
body (Depression…). When the body doesn’t have time to recover from stress and cortisol
levels are high, there are many negative side effects such as sleep disruptions, decreased
muscle mass, blood sugar imbalances, and impaired cognitive performance (Wilson). According
the Scientific American, high cortisol levels in animals shrink the hippocampus (Arkowits).
Although this hasn’t been proven for humans, it’s still a significant discovery. Studies have also
shown that people suffering with depression have a high level of CRH and when they are
exposed to antidepressants these CRH levels are reduced.
Research shows that Serotonin can alleviate symptoms of depression, but not for the reasons
most people believe. Serotonin could have an indirect side effect that stimulates the growth of
brain cells. This is evident in the fact that a boost of serotonin doesn’t have an immediate
effect. It takes several weeks or longer for the patient to feel better because serotonin
promotes the creation of other chemicals that induce in neurogenesis, a process that takes
several weeks. This is supported by a study in Science that gave mice antidepressants for four
weeks. After four they were less anxious and more aggressive when retrieving food from a
bright location. Results showed that the mice had a 60% increase of new cells in the
hippocampus. However, when researchers impeded neurogenesis by dousing the hippocampus
with x-rays, they mice didn’t exhibit any sort of improvement in behavior (Harvard Health).
Therefore, the new approach that is popular today is to prescribe drugs that stimulate
neurogenesis, that in effect will strengthen nerve cell connections and improve the exchange of
information between nerve circuits.
There are many genetic factors that makes someone more vulnerable to depression. One
particular study found that a variation in the serotonin transporter gene, 5-HTT, leaves
individuals to be more prone to depression in response to stress (Depression). Each person has
two copies of the gene; one from their mother and the other from their father which can either
be long or short. Over a five-year period, 800 patients who were exposed to similar stressful life
events, such as the loss of a job or a divorce were tested. It was found that 33% of participants
with one short gene and one long gene became more depressed than participants with two
long genes, but less depressed than participants who had two short genes. Studies of identical
twins also show that if one twin has bipolar disease, then the other twin had a 60-80% chance
of developing the same mental disability. Another gene, CRHR1, provides the code for a stress
hormone, corticotrophin. For a study published in Archives of General Psychiatry, researchers
gathered 621 adults’ who suffered childhood abuse and tested their DNA. Among the 621
adults, the ones who had the protective version of CRHR1 had only half the symptoms of
depression as participants without this genetic variation (Harvard Health). Lastly, the variation
in the DNA sequence, G1463A, had a significant effect on the likelihood of depression. People
with the atypical DNA sequence are more prone to depression.
As the body develops, it generates new cells, each with a copy of the original set of DNA. At
times there can be errors in the copying process, causing a gene mutation. This causes the gene
to code for a slightly different protein. Although most mutations are silent mutations,
sometimes even beneficial, some can lead to disabilities and diseases. However, genes can also
be effected by the environment. Epigenetics studies the changes in organisms caused by a
modification in the gene that either turns on or off to produce a specific protein rather than the
alteration of the genetic code itself (NIMH). In other words, experiences can change the way
DNA functions without changing the code itself. It’s also been shown that epigenetic effects,
such as depression, can be hereditary. Experiments show that exposing mice to severe chronic
stress induced symptoms of depression not only for the initial mouse, but also for the offspring
across future generations(Isabel). Although these are all extraordinary findings, the science
behind these claims are still nascent.
Seasonal Affective Disorder (SAD) is another form of depression caused by the changes of
season. Although it only effects about 2% of the population, research on this form of
depression has uncovered another potential factor contributing to depression. Although the
causes of SAD are still unclear, researchers believe it has to do with the production of a
hormone, melatonin. The human body has an internal clock called the suprachiasmatic nucleus,
a bundle of brain cells. This internal clock regulates many biological patters in the body and
syncs it to the time of day. One way to alleviate depression symptoms is by exposing the patient
to light at intervals that don’t correspond to their biological clock, it rests their clock to match
the new environment (Harvard Health). When they tested this on people with depression,
many of their symptoms were alleviated due to the proper production of melatonin.
Possible Solutions
If one of the factors of depression is the deterioration of brain cells, then the most sensible
solution is to prevent deterioration and promote neurogenesis. Until recently it was believed
that neurogenesis was not possible in an adult brain. Yet, this far from the truth. In fact, the
hippocampus is one of the unique structures in the adult brain where new brain cells can be
created (Thuret). The blue neuron in the picture below is a brand new neuron in the adult
brain. It has been estimated that the brain produces 700 new neurons a day in the
hippocampus. Although this is nothing compared to the 100 billion neurons already in the
brain, by the time we are 50 years old, the brain will have replaced every neuron we were born
with with a new neuron in that structure (Thuret). However, neurogenesis does decline with
age, but there are still possible ways to stimulate it.
Neuroscientist Sandrine Thuret believes that humans can generate new brain cells. Many things
can reduce the natural rate of neurogenesis, such as stress, lack of sleep, and of course aging.
Conversely many things can also increase the rate of neurogenesis, such as learning, sex, and
aerobic activity. The American Psychological Association (APA) found that middle school
students who performed better on cardiorespiratory fitness tests were significantly less likely to
report feeling depressed a year later (American Psychological Association). This is most likely
credited to the growth of new brain cells. The Rusty Gage of the Salk Institute examined how
aerobics facilitate neurogenesis in mice. The controlled mice lacked a wheel in the cages, while
the other group had wheels in their cages. The block dots in the figure below show the
development of new neurons.
Thuret also explains that dietary habits contribute to neurogenesis. Calories restriction of 2030%, intermittent fasting, and omega-3 fatty acids enhance neurogenesis, while alcohol
consumption and high saturated fats halt neurogenesis. According to a study done in 2004,
exposure to hippocampal-dependent learning tasks and voluntary running have shown to
stimulate neurogenesis and increase the chance of survival for new neurons in adults.
Conclusion:
Depression is still an unsolved puzzle. As technology improves and we come to understand
more about the human brain and depression, it’s critical to integrate what we know about
stress, neural networks, neurogenesis, and brain chemistry. Most importantly, it’s crucial that
we keep searching for the missing puzzle pieces.
Work Cited
American Psychological Association. "Physical Fitness Can Help Prevent Young Adolescents'
Depression, Study Finds." ScienceDaily. ScienceDaily, n.d. Web. 25 Sept. 2016.
Arkowitz, Hal, and Scott Lilienfeld O. "Is Depression Just Bad Chemistry?" Scientific American.
N.p., 11 Feb. 2014. Web. 25 Sept. 2016.
Boeree, George. "The Limbic System." The Limbic System. N.p., n.d. Web. 25 Sept. 2016.
"Brain Anatomy." Core Information. Princeton Brain & Spine, 03 June 2016. Web. 25 Sept. 2016.
Depression and the Brain." Healing Walls. N.p., 26 Sept. 2015. Web. 25 Sept. 2016.
Galvan, Veronica, and Kunlin Jin. "Neurogenesis in the Aging Brain." Clinical Interventions in
Aging. Dove Medical Press, Dec. 2007. Web. 25 Sept. 2016.
Harvard Health. "What Causes Depression?" Harvard Health. Harvard Medical School, n.d. Web.
25 Sept. 2016.
Isabelle Mansury. "Cerebrum." Epigenetics and the Human Brain: Where Nurture Meets
Nature. N.p., 25 May 2011. Web. 25 Sept. 2016
Looi Stephen. "Brain Parts Function & Parts of the Brain." Brain Parts Function & Parts of
the Brain. Brain Health and Puzzles, n.d. Web. 25 Sept. 2016.
NIMH » Brain Basics." U.S National Library of Medicine. U.S. National Library of Medicine, n.d.
Web. 25 Sept. 2016.
Thuret, Sandrine. "You Can Grow New Brain Cells. Here's How." Sandrine Thuret:. TED, n.d.
Web. 25 Sept. 2016.
University of Sydney. "Patients with Recurrent Depression Have Smaller Hippocampi." News.
The University of Sydney, 30 June 2015. Web. 25 Sept. 2016.
"What Are Neurotransmitters?" What Are Neurotransmitters? N.p., n.d. Web. 25 Sept. 2016.
Wilson, James. "Cortisol & Adrenal Function." Adrenal Fatigue. Adrenal Fatigue, n.d. Web. 25
Sept. 2016
Photo Bibliography
1. https://a2ua.com/brain/img-001.php?pic=/brain/brain-001.jpg
2. http://www.princetonbrainandspine.com/brain/brain-anatomy/
3. https://www.ted.com/talks/sandrine_thuret_you_can_grow_new_brain_cells_here_s_
how?language=en