Written by Daniel Z. Lieberman, MD
Last updated 8/2/2023
Researchers at Stanford University have discovered a new kind of depression. That may sound about as appealing as discovering a new kind of mold in your refrigerator, but it’s actually good news.
Psychiatrists classify depression as a single illness, but we know that’s an oversimplification. In reality, it’s probably a family of related illnesses that have similar symptoms. The different flavors, or subtypes of depression may require different forms of treatment. For example, seasonal depression, also known as the winter blues, may respond best to therapeutic bright light rather than antidepressant medication.
The newly discovered subtype has been christened the cognitive subtype, characterized by decreased activity in the frontal lobes of the brain. Our frontal lobes help us plan ahead, and allow us to break down complex tasks so they can be accomplished one step at a time. They help us focus and concentrate so we can analyze and understand complex ideas. The frontal lobes, which are larger in humans than in any other animals, also give us self-control. They allow us to suppress instinctive reactions that would be inappropriate to act on.
The cognitive subtype of depression is surprisingly common. It was found in about 27% of the research volunteers who were depressed. These volunteers did poorly on tests of cognition and demonstrated impulsivity on tests that required self-control. Most striking of all, they didn’t respond well to treatment with SSRIs, the most commonly used class of antidepressants.
The treatment of depression is something of a mystery. When different antidepressants are tested in large groups of volunteers, they all seem to have about equal efficacy. But when it comes time to treat a single individual, one antidepressant may do nothing at all, while a similar one leads to a full remission of all symptoms. We don’t know why, and it’s frustrating because it makes treatment a process of trial and error.
Since we can’t predict which antidepressant will be the right one, patients will sometimes have to endure multiple trials of different medications before they find the one that’s right for them. Sometimes, it becomes so frustrating, patients give up and continue living with depression for months or years longer than necessary. Maybe this study reveals part of the answer to this puzzle.
It’s possible that the reason we’re stuck with a process of trial and error is that depression is so heterogeneous that different subtypes require different treatments. Just as a viral infection won’t get better if it’s treated with an antibiotic that kills bacteria, the cognitive subtype of depression may require different treatments than the subtypes that respond to SSRIs.
The discovery of this new subtype is so recent there hasn’t been time yet to study which treatments might work best. Mental health clinicians are often faced with this problem: not enough research has been carried out to guide clinical decision-making.
Research is difficult, expensive, and takes years to get results, so, in the meantime, clinicians must use the intuition they’ve developed from years of practice. In this case, the first medication that comes to my mind, and I suspect my colleagues would agree, is the antidepressant bupropion, sold under the brand name Wellbutrin.
Although there’s no evidence yet for bupropion’s effectiveness in cognitive depression, we know that it boosts the activity of dopamine. That’s the brain chemical used by the frontal lobes to coordinate cognition. Boosting dopamine in the frontal lobes can lead to increased focus, increased concentration, and decreased impulsivity. Clinical trials will be needed to test whether this mechanism will actually bring relief to those who live with cognitive depression.
The brain is the most complex organ in the body. Some say it’s the most complex structure in the universe. It’s miraculous that each one of us carries around this amazing machine inside our heads, but its complexity makes it difficult to understand.
We have a long way to go before we understand the brain as well as some of the other organs in the body, but we’re making progress. Many people who seek care find substantial relief, and illnesses that were once considered untreatable are responding dramatically well to new therapies and medications. The discovery of this new subtype of depression is another important step in understanding illnesses of the brain and learning how to treat them in the most effective way.