Cellular Alterations In Animal Models Of Depression
Animal models of depression have been used to further elucidate the ultastructural and molecular alterations that underlie the morphological changes observed in MDD patients. Most of these models are based on acute or chronic-stress paradigms, as stress is a critical factor in the etiology of depression. In addition, these models have been used to demonstrate that antidepressants can reverse or block the effects of stress on cellular morphology, which might contribute to the therapeutic actions of these agents.
The Behavioral Inhibition System: A Common Cause Of Post
Before we discuss what goes wrong because of concussions, we need to explore how your brain is supposed to work.
Each of us has a behavioral activation system and a behavioral inhibition system. They monitor and reward our behavior. When the behavioral inhibition system gets triggered too often, depression can result.
How Behavioral Activation and Inhibition Work
You can think of the behavioral activation system as our brains default setting. It makes us curious and eager to learn. It helps us feel rewarded for mastering a topic or experiencing something pleasurable. Its an important part of why we engage with the world and the people around us.
But in the background, the behavioral inhibition system is monitoring everything we do. Its watching out for loss, and it tells us whenever weve experienced a loss. And if we experience what it believes are too many losses, it pulls back on the reigns, dampening the behavioral activation system.
For example, think of your activities like investments in the stock market. If you invest in stocks and win, you feel great! When you lose, you feel disappointed or maybe even regretful. But when you lose money repeatedly, you might start to reconsider your investments you might even pull out of the stock market altogether because the cost to you is just too high, and there is little or no return on your investments.
How Behavioral Inhibition Leads to Depression After a Concussion
What If Youve Had Depression Before?
Structural And Connective Changes
As mentioned earlier, depression can cause shrinkage to specific areas of the brain and therefore cause their dysfunction.
For example, reduced functionality of the prefrontal cortex can affect their executive function and attention, dysfunction of the amygdala can affect emotional regulation and mood, and reduced hippocampal functionality can cause memory issues.
These changes usually take a minimum of 8 months to develop and may persist for longer periods after longer-lasting depressive episodes, particularly affecting memory emotional regulation, mood, and attention.
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Can Brain Changes That Occur In Chronic Depression Be Reversed
In this video, Greg Mattingly, MD, discusses how some of the neurological impacts of chronic depression can possibly be reversed. Dr. Mattingly is Associate Clinical Professor, Washington University, St. Louis, Missouri, principal investigator in clinical trials for Midwest Research Group and founding partner of St. Charles Psychiatric Associates, St. Charles, Missouri.
Read the transcript:
Chronic depression causes damage within neural networks in the brain. As we’ve talked about before, chronic depression causes decreased neural connectivity, where one set of neural cells doesn’t crosstalk to another set of nerve cells.
Pioneering work by Yvette Sheline, Wayne Drevets, and others has shown the chronic depression decreases the size of the hippocampus, damages parts of the anterior cingulate and other pathways within the brain.
The good news is, some of this damage can be reversed. We have wonderful new information about the role of neural networks, about the role of neural growth factors.
I’d like to go back in time. One of the reasons that I chose to go into neuroscience, chose to go into psychiatry, was in 1986, the Nobel Prize was awarded for the discovery of neural growth factor. That pioneering work was done by some researchers whose lab was at my university, at Washington University. For the women in the audience, Rita Montalcini was the first woman to win a Nobel Prize in neural science.
More with Dr. Mattingly:
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.
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How Stress Affects The Body
Stress can be defined as an automatic physical response to any stimulus that requires you to adjust to change. Every real or perceived threat to your body triggers a cascade of stress hormones that produces physiological changes. We all know the sensations: your heart pounds, muscles tense, breathing quickens, and beads of sweat appear. This is known as the stress response.
The stress response starts with a signal from the part of your brain known as the hypothalamus. The hypothalamus joins the pituitary gland and the adrenal glands to form a trio known as the hypothalamic-pituitary-adrenal axis, which governs a multitude of hormonal activities in the body and may play a role in depression as well.
When a physical or emotional threat looms, the hypothalamus secretes corticotropin-releasing hormone , which has the job of rousing your body. Hormones are complex chemicals that carry messages to organs or groups of cells throughout the body and trigger certain responses. CRH follows a pathway to your pituitary gland, where it stimulates the secretion of adrenocorticotropic hormone , which pulses into your bloodstream. When ACTH reaches your adrenal glands, it prompts the release of cortisol.
The boost in cortisol readies your body to fight or flee. Your heart beats faster up to five times as quickly as normal and your blood pressure rises. Your breath quickens as your body takes in extra oxygen. Sharpened senses, such as sight and hearing, make you more alert.
Ways To Cope With Depression After Brain Injury
Weve put together some top tips to help cope with depression
Depression is common among brain injury survivors, with half of all survivors experiencing it in the first year following their injury.
It can also develop as the person starts to understand the full impact of their injury, and can lead to feelings of hopelessness and altered self-esteem and identity as the survivor reflects over the changes that they are facing, and may continue to face in the future.
With expert support from Dr Elizabeth Kent and Dr Cliodhna Carroll, from Kent Clinical Neuropsychology Service, and with feedback from brain injury survivors, weve put together some top tips to help cope with depression.
More detailed information can be found on our factsheet Depression after brain injury.
The information provided here is not intended to replace medical advice, so if you are experiencing symptoms of depression always speak to your GP or other healthcare professional.
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People Suffering From Depression Run The Risk That Their Brains Shrink And Will Remain Smaller After The Disease Is Over The Discovery Provides New Knowledge About The Brain And New Understanding Of How Antidepressants Work
A depression not only makes a person feel sad and dejected it can also damage the brain permanently, so the person has difficulties remembering and concentrating once the disease is over. Up to 20 percent of depression patients never make a full recovery.
These are the conclusions of two projects conducted by Professor Poul Videbech, a specialist in psychiatry at the Centre for Psychiatric Research at Aarhus University Hospital.
In one of the projects he scanned the brains of people suffering from depression, and in the other he conducted a systematic review of all the scientific literature on the subject.
My review shows that a depression leaves its mark on the brain as it results in a ten percent reduction of the hippocampus, he says. In some cases, this reduction continues when the depression itself is over.
Antidepressants can help
What Does Major Depression Do To The Brain
Depression is more than just a mood disorder. It is a psychological condition that affects more than just the way you feel. Major depression, also known as clinical depression, can cause the chemical activity of your brain to change resulting in numerous different symptoms. So, how exactly does depression impact the brain? Keep reading to find out!
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Let Us Help You Restore Your Brains Health
Here at StoneRidge Centers, we aim to restore the brain to its optimal state of health. Our comprehensive curriculum combines evidence-based therapy, nutrition, and exercise. Anxiety and depression dont have to control your life. Our expert staff members can help treat mental health and addiction challenges.
We can help you manage anxiety and depression in a healthy way that will prevent further harm to your brain. Contact us today at 928-583-7799 if you or a loved one are living with anxiety or depression. Were available 24 hours and 7 days a week to answer any questions you may have.
Disrupted Sleep And Other Symptoms: Reinforcing Depressive Feelings
While theyre not often a direct cause, other symptoms of concussion can work in concert with your loss system to worsen or reinforce depressive symptoms. Many post-concussion syndrome patients experience disruption to their sleep, and sleep deprivation itself can result in depressive symptoms. Additionally, the symptoms of depression can make it harder to sleep, so they work together to make everything feel worse.
Being in pain all the time is another factor. Its harder for your brain to believe its safe to go back to normal if its busy reacting to headaches, feelings of overwhelm, brain fog, and so forth.
Finally, all this can lead to altered habits that further contribute to the depressed state. Even though it may be difficult, try to eat well, rest as best you can, and exercise regularly .
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Untreated Mental Disorders Cause Shrinkage Of Key Brain Areas
2. Damage from Disorders
The second thing that has become clear from New Neuropsychiatry research is that psychiatric disorders are bad for your brain. Study after study show that clinical depression and anxiety disordersnot to mention severe conditions like schizophrenia and bipolar disorder and drug abusecause measurable changes in key areas of the brain.
This isn’t just an abstract issue it is a serious and meaningful issue for people who have mood and anxiety disorders. Take depression as an example: Common symptoms include mood changes but also difficulty with cognitive functioningtrouble remembering things, difficulty making decisions, planning, setting priorities, and taking action. These are symptoms that every therapist and psychiatrist, and other doctors, see on a daily basis in people with depression. Brain imaging studies using MRI scanning show that these common day-to-day depression symptoms are associated with abnormalities in specific areas of the brain, including the hippocampus , the anterior cingulate , and the prefrontal cortex .
Susceptibility To Physical Health Issues And Illness
Stress hormones make your heart beat faster as if youre constantly in danger. Because your heart isnt meant to beat at high speeds for extended periods, this could lead to a life-threatening heart illness in the future.
Depression also impacts your digestive systems health, especially if you binge eat or take antidepressant medications. If you rapidly gain weight during a depressive episode, youre more likely to develop diseases closely tied to obesity, like diabetes. Conversely, depression may also cause someone to lose their appetite for food and experience rapid weight loss, which can be equally harmful to the body.
Some people may use drugs or alcohol as a way to deal with their symptoms of depression, leading to substance use disorders. In some cases, this substance abuse issue can develop into life-threatening addictions.
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A Long Road To Understanding Depression
For years and years, doctors and researchers assumed that depression stemmed from an abnormality within these neurotransmitters, particularly serotonin or norepinephrine. But over time, these two neurotransmitters did not seem to account for the symptoms associated with major depression. As a result, doctors began to look elsewhere.
The search proved fruitful. There are chemical messengers, which include glutamate and GABA, between the nerve cells in the higher centers of the brain involved in regulating mood and emotion, says John Krystal, MD, chair of Yales Department of Psychiatry, noting that these may be alternative causes for the symptoms of depression.
These two are the brains most common neurotransmitters. They regulate how the brain changes and develops over a lifetime. When a person experiences chronic stress and anxiety, some of these connections between nerve cells break apart. As a result, communication between the affected cells becomes noisy, according to Dr. Krystal. And its this noise, along with the overall loss of connections, that many believe contribute to the biology of depression.
There are clear differences between a healthy brain and a depressed brain, Dr. Katz says. And the exciting thing is, when you treat that depression effectively, the brain goes back to looking like a healthy brain.
In this video, Drs. Katz and Krystal explain how depression affects the brain.
When Somethings Wrong But Its Not Depression
Sometimes, patients feel down but arent experiencing depression. In these cases, theyre often aware that theyre not exactly depressed, but that theres still something wrong. Often, what theyre really experiencing is grief.
You may be familiar with the five facets of grief: denial, bargaining, anger, sadness, and acceptance. Not everyone experiences all five, and they might not experience them in that order they might bounce back and forth between the five facets.
The sadness stage of grief has some similarities to clinical depression: You may experience feelings of loss, emptiness, and sadness. You might even experience some disinterest. But key differences between grief and depression are feelings of worthlessness, low motivation, apathy, meaninglessness, hopelessness, and suicidal thoughts. Depression sufferers often have these features whereas those suffering from grief generally dont.
When grief is at the heart of your mood, your depression-like symptoms often will resolve more quickly than depression once youve been through treatment for post-concussion syndrome. Because grief doesnt activate the behavioral inhibition system as strongly as depression does, these patients often have an easier time experiencing reward and joy from returning to normal activities.
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What Is Major Depression
Major depression, or major depressive disorder, is a mood disorder and mental illness that causes significantly and persistently low moods. More than just feeling down for a day or two, depression causes a bad mood that you cant shake for weeks. Some of the key symptoms and signs of depression are:
- Persistent feelings of sadness and hopelessness
- Loss of interest in activities you normally enjoy
- Difficulty sleeping or sleeping too much
- Weight gain or weight loss
- Extreme fatigue
- Anxiety, restlessness, frustration, or irritability
- Feeling worthless, guilty, or ashamed
- Difficulty concentrating, making decisions, or remembering
- Thoughts of suicide and death
You may be diagnosed with depression if you have some of these symptoms for a couple weeks or longer, if they are severe enough to disrupt your normal functioning, and if they cannot be explained by substance abuse, medications, or an illness.
Stress Shrinks The Brain
Even among otherwise healthy people, stress can lead to shrinkage in areas of the brain associated with the regulation of emotions, metabolism, and memory.
While people often associate negative outcomes to sudden, intense stress created by life-altering events , researchers actually suggest that it is the everyday stress that we all seem to face that, over time, can contribute to a wide range of mental disorders.
In one study, researchers from Yale University looked at 100 healthy participants who provided information about the stressful events in their lives. The researchers observed that exposure to stress, even very recent stress, led smaller gray matter in the prefrontal cortex, a region of the brain linked to such things as self-control and emotions.
Chronic, everyday stress appeared to have little impact on brain volume on its own but may make people more vulnerable to brain shrinkage when they are faced with intense, traumatic stressors.
The accumulation of stressful life events may make it more challenging for these individuals to deal with future stress, particularly if the next demanding event requires effortful control, emotion regulation, or integrated social processing to overcome it, explained the studys lead author, Emily Ansell.
Different kinds of stress affect the brain in different ways. Recent stressful events affect emotional awareness. Traumatic events have a greater impact on mood centers.
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Regions That Affect Mood
Increasingly sophisticated forms of brain imaging such as positron emission tomography , single-photon emission computed tomography , and functional magnetic resonance imaging 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 .
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 in the hippocampus.