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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