How Depression Affects the Brain

How Depression Affects the Brain

The consequences of depression and major depressive disorder, also known as clinical depression, on the brain are rather complicated. While we still don’t fully comprehend the connection between depression and our brains, it is known that depression can cause physical changes ranging from inflammation to shrinkage.

Emotions and feelings, or the lack of emotions and sensations for some, come to mind when we think about depression. However, it’s critical to be aware that depression also includes physical components. In terms of a person’s behavior, most people know what depression looks like on the surface, but medical knowledge of the disease’s actual course and available therapies is still developing.

The physical makeup of your brain is altered when you have depression. According to National Institutes of Health research, depression causes a loss in gray matter volume (GMV). This loss results from areas of your brain shrinking due to the stress hormone cortisol preventing brain cell proliferation. A person loses more GMV as their depression becomes more severe. Your GMV comprises most of your neurons or nerve cells; delayed growth indicates a risk of cognitive impairment.

It’s vital to get treatment for depression because repeated incidents tend to erode your brain’s structure over time. However, you may be able to avoid or mitigate some of the following changes with early therapy.

Today, we know that neurotransmitters, which may be thought of as the messengers that transfer messages between brain cells or neurons, have a role in depression on a chemical level.

Brain Shrinkage

There is mounting proof that depression causes numerous brain regions to shrink. The extent to which some locations are impacted is up for discussion. These regions lose GMV, which has a lot of brain cells. People with chronic or continuous depression appear to experience more significant GMV loss. Additionally, you could speak slowly, move slowly, or overreact when you feel bad. The GMV rises in proportion to the severity of the depression.

According to studies, depression can reduce GMV in the following areas:


The hippocampus is sensitive to stress hormones and connected to other areas of the brain that regulate emotion. Because of this, depression can affect it. The hippocampus is responsible for several brain processes. It’s in charge of things like learning, memory storage, emotions, and stress (connecting other parts that process emotions and anxiety). When it comes to processing long-term memory and recollection, the hippocampus is crucial.


The thalamus receives the majority of sensory data from the brain. It participates in many complex processes, including speech, cognition, behavioral reactions, learning, and movement. Depression can impact the thalamus, which can shrink in those diagnosed with the disorder since it links sensory input to positive and negative sensations.


The insula aids in both routine and automatic tasks. It may impact our experiences with love, pain, cravings, general emotions, addiction, and more. It transmits sensory information from the body and the world outside. To put it briefly, the insular cortex connects our sensory perceptions and emotional reactions. It controls the immune system and affects taste as well. The insula appears smaller in depressed individuals, similar to the prefrontal cortex, thalamus, and caudate nucleus.

Prefrontal Cortex

The prefrontal cortex primarily controls high-level planning and thinking. The prefrontal cortex was found unusually low in several brain scans of depressed individuals. Furthermore, the degree of prefrontal brain activity reduction seems to correlate with the severity of depression.

Additionally, there is evidence that specific brain regions shrink, including the insula, thalamus, caudate nucleus, and amygdala.

When these sections aren’t functioning correctly, you might experience:

  • Anxiety
  • Memory issues
  • Inability to think clearly
  • Either guilt or despair
  • Lack of motivation
  • Problems with eating or sleeping


According to researchers, low concentrations of specific neurotransmitter molecules may be related to depression. Your body’s chemical messengers are called neurotransmitters. They transfer information from one nerve cell to the next neuron, muscle, or gland cell by traveling over a distance. These signals aid in the movement of your limbs, perception of sensations, maintenance of heartbeat, and the assimilation and processing of all the information your body gets from other internal organs and the surroundings.

What Are Neurotransmitters?

Your body cannot operate without neurotransmitters. They are responsible for transmitting chemical signals, or “messages,” from one neuron (nerve cell) to the following target cell. Another nerve cell, a cell of the muscle, or a cell of a gland may be the next target cell.

Your nervous system, an extensive network of nerves in your body, transmits and receives electrical messages between nerve cells that transport across the entire body. Everything in your body, including your muscles, intellect, and organs, is under the direction of your neurological system. In other words, everything you do, think, and feel is influenced by your nerves. Information is sent and received by your nerve cells from every body part. Your body needs this regular input to operate at its best.

Your nervous system is in charge of managing bodily operations such as:

  • Blood pressure and heartbeat
  • Breathing
  • Muscle motions
  • Sensations, memories, learning, and thoughts
  • Aging, recovery, and sleep
  • Stress reaction
  • Hormone control
  • Digestion, a hungry or thirst pang
  • Senses

Low Neurotransmitters

The quantity of brain nerve cell communication decreases with reduced neurotransmitter levels. When this occurs, the brain cannot get the messages required to know when to engage in certain behaviors, such as fight or flight, pleasure, sleeping, eating, lessening pain, or reducing worry. Due to this separation, people can suffer depressive symptoms like sleeplessness, loss of appetite, or irritability.

Aspects of depression are also linked to low levels of norepinephrine, serotonin, and dopamine. There is a higher risk of developing depressive symptoms when someone’s system generates low quantities of these neurotransmitters.


It impacts the brain regions in charge of regulating attention and activity. Additionally, it is linked to the fight-or-flight response and can raise heart rate, release glucose from energy reserves, and boost blood supply to skeletal muscles. The brain’s locus coeruleus becomes active under stressful situations, which results in the release of norepinephrine and other physiological changes.

Norepinephrine release could significantly impact a substantial portion of the brain, which is why it has been used clinically to treat mental problems. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are antidepressants that are frequently given to treat the symptoms of anxiety, depression, and occasionally attention deficit hyperactivity disorder (ADHD).


When the serotonin levels in your brain are low, you may experience a decrease in happiness or well-being. Naturally, that might leave you hopeless, nervous, annoyed, and feeling unworthy — all signs of depression. Other indications of depression may also appear. Your entire body is affected by serotonin, including your emotions and motor abilities. Serotonin is considered a natural mood creator. It is a substance that facilitates eating, sleeping, and digestion.

Medical professionals frequently prescribe selective serotonin reuptake inhibitors (SSRIs) to treat depression. They are the kind of antidepressant that is most commonly administered. By preventing the chemical’s reabsorption, SSRIs raise serotonin levels in the brain by ensuring that more of it is kept active. Prozac and Zoloft are two examples of SSRIs.


Depression, Parkinson’s disease, and restless legs syndrome are all related to low dopamine levels. Dopamine is a neurotransmitter and a hormone. Dopamine deficiency can cause various symptoms, including fatigue, moodiness, and lack of motivation. Memory, learning, rewards, and movement are just a few of the many bodily processes that dopamine supports.

The neurotransmitter dopamine is produced in some areas of the brain. If the parts of your brain that produce dopamine are damaged, you might have low amounts of the chemical. Likewise, if your body doesn’t react to dopamine appropriately (if there’s an issue with the nerve cell receptors that take in and transmit the chemical message), you can also have low levels of dopamine.

Selective serotonin uptake inhibitors, such as fluoxetine (Prozac), that influence the neurotransmitters serotonin and dopamine to make them active, may be used to treat depression.

Inflammation of the Brain

Some researchers believe that inflammation promotes susceptibility to depression.

Untreated inflammation in the brain can:

  • Destroy or damage brain cells
  • Prevent the development of new brain cells
  • Cause cognitive difficulties
  • Accelerate the aging of the brain

However, the results of a study published in 2022 indicate that depression in many older adults occurs independently of inflammation. Researchers said their data suggest that depression comprises different subcategories, some with inflammation and others without. They allowed for the possibility that inflammatory disorders may contribute to depression.

Translocator protein levels (TSPOs)appear to be even more significant in those who experience a severe depressive disorder. Increased TSPO binding is linked with suicidal thoughts and inflammation in the brain. Studies have shown that these proteins are considerably greater in individuals who have had severe, untreated depression for 10 years or more.

Are Brain Changes Long-Term?

That question still has researchers working to find an answer. Long-term brain alterations, particularly in the hippocampus, are probably brought on by persistent depression. That may be why some people find it difficult to recover from depression. However, according to the findings, those with a lifelong major depressive disorder diagnosis who had not experienced depression in years also had lower gray matter volumes.

There is optimism that existing or novel therapies may help reverse or prevent some brain abnormalities, while further study is required.

The results of studies on two popular depression therapies are as follows:


These affect the brain chemicals that regulate stress and emotions. There is proof that these medications can reduce inflammation and aid in neuroplasticity and the formation of new brain connections. To regulate stress and emotional hormones, antidepressant drugs contain substances that have been scientifically developed. They function by reducing inflammation and encouraging the development of new connections between neurons.

Cognitive Behavior Therapy (CBT)

Neuroplasticity can also be also encouraged through cognitive behavior therapy, which increases the brain’s adaptability and capacity to develop new neural connections. It has been demonstrated that in certain circumstances, this type of talk therapy is just as effective — if not more effective — than medicine.

CBT can be effective for people suffering from mild to moderate depression. However, for more severe instances, a combination of CBT plus medication like antidepressants has been demonstrated to be quite beneficial in lowering depression symptoms while enhancing the overall quality of life.

Ways to Get Help

If you experience any signs of depression, let your doctor know. To determine the best course of therapy for you, they’ll want to rule out any other medical concerns, such as hypothyroidism. Your lifestyle may need to change, you may need to take medication, or you may need to consult a mental health professional. A combination of all three works well for some folks.

For mild or severe depression, treatments include:

  • Antidepressants
  • Talk therapy
  • Short-term ketamine usage
  • Brain stimulation
  • Exercise
  • Meditation
  • Diet changes


Although depression is a severe mental health problem, its direct impact on brain activity is still not well understood. Several parts of depressed individuals’ brains are often more active than those of healthy, non-depressed people.

It’s possible that a variety of brain areas influence the various depression symptoms. Human brain imaging investigations, which are still in their early phases, have shown alterations in blood flow or other associated measurements in many brain regions, including the prefrontal and cingulate cortex, the hippocampus, the amygdala, and the thalamus, to name a few. These biological results align with behavioral findings that depressed individuals exhibit a negative cognitive bias in which unfortunate events are seen as more significant than positive ones.


Medically Reviewed By:

Robert Gerchalk

Robert is our health care professional reviewer of this website. He worked for many years in mental health and substance abuse facilities in Florida, as well as in home health (medical and psychiatric), and took care of people with medical and addictions problems at The Johns Hopkins Hospital in Baltimore. He has a nursing and business/technology degrees from The Johns Hopkins University.

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