What does depression do to your brain?

We’ve all had the blues from time to time, but what happens when the blues turn into something more?

Depression is a common mental disorder. About 29% of American adults reported having been diagnosed with depression at some point in their lives, according to a 2023 Gallup survey. Depression in its more severe form, major depression, is a source of serious impairment and disability.

You might not realize it, but depression can actually change your brain physically.

“That’s what happens if the depression is severe and goes without treatment for long periods,” said Joshua L. Straus, FACLP, DLFAPA, a board-certified psychiatrist with Endeavor Health Medical Group in Evanston, and Division Director of Neuromodulation and Medical Director of Transcranial Magnetic Stimulation.  

“I would say that is not the rule for ordinary depression, but comes into play for persons having a great number of severe episodes of depression,” he added.

Long-lasting depression and the brain

This kind of severe and long-lasting depression can cause higher rates of brain inflammation, dysfunction in key brain circuits and reduced volumes of gray matter in the brain.

Brain inflammation from long-lasting depression is linked to dysfunction of the glial cells that support brain neurons. This dysfunction triggers a cascade of cell-signaling events in the brain, with higher levels of cytokines, interleukins, translocator proteins and other inflammatory-signaling molecules sustaining the inflammation. These processes may damage or destroy brain cells and prevent new cells from growing, accelerating brain aging.

More familiar neurotransmitters are chemicals like serotonin, dopamine and norepinephrine. But there are many other neurotransmitters — hundreds in fact — that are known to be very important. Some are the basis for some newer medications for the treatment of major depression, such as glutamate. Depression can cause key circuits that communicate using these neurotransmitters to malfunction.

If you were to do a PET scan of a depressed person’s brain, often you would see less activity in the left dorsolateral prefrontal cortex. It is this region of the brain that is widely connected to other areas involved in mood regulation, and when these circuits remain at a very low level of activity, depression symptoms often emerge.

“The brain is an electrochemical organ, so the stuff you may hear from time to time about a ‘chemical imbalance’ in the brain as the cause of depression is just wrong,” Dr. Straus said. “I don’t know who came up with it, but it’s really unhelpful. You need the right amount of the right neurotransmitter in the right circuit at just the right time for these electrochemical neuronal circuits to work properly. The brain is an incredibly complicated and beautiful thing.”

Ready for another bombshell? There’s more serotonin in your bowel than in your brain — by a lot. “Almost every neurotransmitter that’s in the brain is in the gut as well. And in large amounts,” he said.

Tracking depression symptoms

It’s important to note that not all depression progresses to the need for treatment, and mild events are often self-limiting (resolve on their own) or are managed with psychotherapy or counseling alone.

Much like you would watch a low-grade fever, very mild depression is important to note and track, Dr. Straus said. For example, if someone goes from 100 F to 103 F and has a serious cough and shortness of breath, it should trigger urgent medical evaluation. The same holds true for depression.

We use standardized depression rating scales, like the PHQ-9, similar to a thermometer, he said. It does not substitute for a full evaluation but is very good at showing when major depression is getting worse, and is a very helpful too to start considering all the possible reasons that depression might be worsening.

Sometimes it’s a medication that may be causing adverse psychological side effects. Everything from prednisone to OTC cold and flu remedies, can negatively affect mood and behavior.

Treatments to relieve depression

What can people do to feel better? The good news is that there are excellent treatments for depression.

Roughly two-thirds of depressed people get better just with antidepressant medication, Dr. Straus said. Over 80 percent of people will find some improvement for major depression using a combination of antidepressant psychotherapy, medications and/or neuromodulation treatments like TMS and ECT. Full remission is admittedly harder to achieve, Dr. Straus said, but it is the goal for every patient with major depression.

We also depend on the brain healing itself, Dr. Straus said. “I like to say you can provide conducive conditions for brain healing,” he added. “I tell all my patients about the importance of sticking with good sleep patterns, a balanced diet and exercise, all of which supports the specific antidepressant treatments I prescribe to work properly.”

“Our treatments tend to promote the natural healing process,” he said. “Even with psychotherapy, there are re-connections happening. With functional neuroimaging studies, you actually see the brain come back online as people respond to cognitive behavioral therapy with no medication, or with medication, electro-convulsive therapy (ECT), or transcranial magnetic stimulation (TMS) where we use magnetic fields to induce small electrical currents within key circuits of the brain.”

“The bottom line is, there are lots of different causes and lots of available treatments for depression — and treatment helps,” he said.

Dr. Straus treats patients with major depression, bipolar depression, treatment-resistant depression, psychiatric complications of cancer and other complex medical illness and a range of other psychiatric disorders.

If you’re feeling sad, if you’ve lost interest in activities that you once enjoyed, if you’re eating more or less than usual, if you’re sleeping too much or not enough, if you have difficulty concentrating and if you’re thinking about death or suicide, you could be suffering from depression.

Endeavor Health behavioral health experts are here to support you. Learn more.

If you’re having suicidal thoughts or having a mental health crisis, help is available. In the U.S., call or text 988 or chat at 988lifeline.org to reach the 988 Suicide and Crisis Lifeline. For Spanish language, call (888) 628-9454.