How Does Depression Affect The Brain?

When we think of depression, what comes to mind may be feelings and emotions or negative thoughts.

But while those are symptoms of depression, a depressive disorder may physically change our brain as well.

Beyond negatively impacting our thoughts and mood, though, exactly how does depression affect the brain?

While the physical symptoms of depression are sometimes more noticeable, the effects of depression on the brain might be more of a mystery to some.

We’ve covered all the information on how depression affects the brain as well as possible ways to reverse the effects and treatment options.

Major depressive disorder, more commonly referred to as major depression or just depression, is one of the most common mood disorders.

So common, in fact, that the National Institute of Mental Health (NIMH) estimated that 21 million U.S. adults had at least one major depressive episode in 2020.

A depressive disorder is characterized as a period of at least two weeks when someone experiences a depressed mood or loss of interest or pleasure in everyday activities.

Someone with major depression may also experience several depressive symptoms, such as problems with sleep, energy or concentration.

Other common symptoms of depression include:

• Persistent feelings of sadness, tearfulness, anxiety, hopelessness and/or an “empty” mood

• Irritability and anger, frustrated outbursts over minor issues

• Reduced appetite and weight loss

• Increased appetite, food cravings and weight gain

• Feelings of restlessness, anxiety and agitation

• Noticeably slower speech and movement

• Physical pain and other physical symptoms, including headaches, joint and/or muscle pain and digestive problems

• Recurrent thoughts of death, suicidal thoughts and suicide attempts

Depression symptoms can vary in severity as well as how long they last and reoccur.

There are also several different types of depression such as:

• Seasonal affective disorder (SAD)

• Persistent depressive disorder (Dysthymia)

• Bipolar disorder

• Postpartum depression

Our guide to depression goes more in-depth on the different types of depression.

Like other mental health conditions, depression is caused by multiple conditions. While the exact cause of depression is unknown, medical professionals believe brain chemicals (or neurotransmitters) play a part in depression.

These chemicals are responsible for transmitting information between nerve cells as well as regulating countless functions in the body, like sleep, metabolism and mood.

So, how does depression affect the brain?

A 2021 review on the current neuroscience research surrounding major depressive disorder found differences in brain volume and activity when it comes to depressed brains and non-depressed brains.

Brain Shrinkage

A small 2018 study showed that specific regions of the brain can decrease in size in people who experience depression.

A 2018 study showed that the following parts of the brain can be affected:

• Hippocampus. The hippocampus plays an important role in memory and learning. Prolonged depression has been associated with atrophy of the hippocampus, causing it to waste away.

• Thalamus. The thalamus relays information from the cerebral cortex, which is the brain’s outer layer, to the brain stem.

• Amygdala. The amygdala regulates emotion and memory.

• Prefrontal cortex. The prefrontal cortex is responsible for cognitive functions, decision making and social behavior.

When a section of the brain shrinks, the ability to perform the functions associated with that particular section declines.

For example, the amygdala and prefrontal cortex work together to control emotional responses.

According to a small 2010 study, shrinkage of those areas can potentially contribute to a reduction in empathy in individuals with postpartum depression. The lack of empathy could be due to other cognitive and emotional issues caused by depression.

An older 2008 study found that amygdala-prefrontal cortex dysfunction may cause the following symptoms in nearly all people with depression:

• Anhedonia, or the loss of interest in activities you once enjoyed

• Dysfunction in the way emotion is perceived

• Loss of adequate emotional regulation

While more research is needed, many medical professionals currently believe that the amount these areas shrink is linked to the severity and length of the depressive episode.

Brain Inflammation

Research has also found a connection between inflammation and depression.

Unusual immune system activity occurs in some people with depression. But it’s still unclear whether depression causes inflammation or vice versa.

Brain inflammation during depression is related to the amount of time a person has been depressed.

A small 2018 study found that people who went untreated for major depression for more than 10 years had 29 percent to 33 percent more translocator protein total distribution volume when compared with people who were depressed and untreated for less time. Translocator protein total distribution volume is an indicator of brain inflammation.

Brain inflammation can cause brain cells to die, leading to several complications.

These include reduced neuroplasticity, which is the ability of the brain to change as a person ages, and reduced functioning of neurotransmitters.

Brain Structure

The central nervous system uses neurotransmitters to relay messages between neurons and other cells within the body.

Three main types of neurotransmitters are excitatory, inhibitory and modulatory.

Several neurotransmitters are associated with depression. A 2018 review linked depression and anxiety in some individuals with low levels of neurotransmitters such as:

• Serotonin

• Dopamine

• Norepinephrine

These three neurotransmitters can affect your mood, thoughts, energy levels and more.

More specifically, serotonin regulates your mood, sleep and multiple other bodily functions and is often referred to as the “feel-good” chemical.

Norepinephrine increases alertness and attention and is part of the body’s “fight-or-flight” response to stress or perceived danger. Dopamine is involved in pleasure, motivation, mood and attention.

A 2017 review found that an unusual balance between excitatory and inhibitory neurotransmitters may occur during depression, but can be reversed upon recovery from depression.

Brain circuits — a network of neurons — are also affected by depression. According to research, not only were certain circuits affected by depression but the impairment of these circuits may also be caused by depression.

Brain Connectivity

Brain connectivity is the way that different regions of the brain interact with one another.

A 2015 review found hypoconnectivity (little connectivity) in the brain’s frontal and parietal lobes, which play a role in attention and the regulation of emotions.

According to another 2015 study, hyperconnectivity, or lots of connectivity, was observed in the frontal and parietal lobes of the brain of adolescents with depression.

According to a 2018 review, connective changes may also result in symptoms such as dysphoria (or a negative mood), anhedonia and rumination.

Research suggests that some of the physical brain changes caused by depression can be reversed.

Early studies have shown promising research that treatments such as antidepressants and cognitive behavioral therapy may reduce inflammation caused by depression as well as help the brain form new synaptic connections that were compromised during depression.

Ketamine and benzodiazepine-like molecules are also promising, according to a 2017 review of human studies of ketamine. This research focused primarily on the activity of glutamate, a neurotransmitter, in the prefrontal cortex.

More research is needed on the potential opioid-like properties of ketamine.

Whether through therapy, medication, lifestyle changes or a combination, there are treatment options for depression.

Going to Therapy

Therapy, or “talk therapy”, has been proven to be an effective treatment for depression.

As part of psychotherapy, you’ll talk with a qualified mental health care professional to identify and overcome the factors that may be contributing to your depression.

Therapy may help you:

• Work out how to solve problems and manage difficulties.

• Identify beliefs, behaviors and thought processes that contribute to depression symptoms and work to replace them with new ones.

• Create healthy behaviors for dealing with setbacks, difficulties and distress.

• Set achievable, realistic goals you can work towards.

Several different types of therapy are used to treat depression, including interpersonal therapy and cognitive-behavioral therapy (CBT).

Taking Antidepressants

Depression is commonly treated using medications called antidepressants which work by changing the levels of certain neurotransmitters in your brain. 

Common antidepressants used to treat major depressive disorder and other forms of depression include:

• Selective serotonin reuptake inhibitors (SSRIs).SSRIs are typically used as first-line medications for treating depression in adults. Common SSRIs include fluoxetine (Prozac®), escitalopram (Lexapro®) and sertraline (Zoloft®).

• Serotonin-norepinephrine reuptake inhibitors (SNRIs). A relatively newer class of antidepressants, SNRIs are used to treat depression and other conditions such as certain anxiety disorders. Common SNRIs include venlafaxine (Effexor®) and duloxetine (Cymbalta®).

• Tricyclic antidepressants (TCAs).Tricyclic antidepressants are an older class of antidepressants not typically used as a first option for treating depression. They may be prescribed if other, newer antidepressants aren’t effective. Examples of TCAs include amitriptyline (Elavil®) and doxepin (Sinequan®).

• Atypical antidepressants. Certain antidepressants are referred to as atypical, as they don’t fit into the categories listed above. A common atypical antidepressant is bupropion (Wellbutrin XL®).

When used for several months, most antidepressants are effective at reducing the severity of depression symptoms.

Several antidepressants may need to be tried before you find the medication that works best for you.

Exercising Regularly

A depressive disorder can’t solely be treated by exercise alone. However, in combination with medication or therapy, regular exercise can help with psychological symptoms and brain changes in treating depression.

A 2020 study suggests exercise can help improve the structure of the hippocampus and activate brain function, among other benefits.

Try exercising daily while you’re being treated for depression, even if it’s just a short walk or yoga flow.

Avoid Drinking Alcohol

Research has shown that people who consume alcohol excessively are more likely to develop depressive disorders and symptoms than those who either drink responsibly or rarely drink.

Especially as alcohol may negatively interact with certain antidepressants, it may be best to either avoid completely or strictly limit your consumption of alcohol.

Looking For Signs

It’s important to be aware of warning signs that may trigger or worsen your depression symptoms. If you find your symptoms getting worse, contact your healthcare provider quickly.

You can also read our guide on more specific signs of depression in women for more information.

Seeking Out Support

There are numerous support groups for people with depression that can give you a social network to assist with your recovery.

Options include NAMI Connection Recovery Support Group (a free, peer-led network of support groups across the country), the ADAA’s network of support groups and local support groups that may meet in your area.

Depression is treatable, and reaching out for help is the first step toward recovery. It’s particularly important to seek help if your depression is starting to interfere with your daily life.

If you experience any of the symptoms above and believe that you’re depressed, it’s best to speak with a mental health professional as soon as possible.