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Experts say six newly discovered subtypes for depression could help determine treatments in the future. Oriol Llauradó Ballesta/Stocksy
  • Researchers say they have identified six different subtypes of major depression.
  • They note that about 30% of people with depression do not adequately respond to treatment.
  • They say the subtypes may help identify potential treatment responses for things such as antidepressants and talk therapy.

A fMRI (functional MRI) might be able to identify six types of depression and identify treatments as more or less likely to work for three of those subtypes.

That’s according to a study completed at Stanford Medicine in California and published today in the journal Nature Medicine.

The study included 801 participants previously diagnosed with depression or anxiety. The researchers used fMRI to measure brain activity at rest and, when people are engaged in tasks, to analyze cognitive and emotional functioning.

The researchers focused on brain regions and their connections and grouped images to identify six distinct activity patterns.

Additionally, 250 participants were randomly assigned to receive one of three commonly used antidepressants or behavioral talk therapy.

The study findings included:

  • Compared to other subtypes, people with one subtype characterized by overactivity in cognitive regions of the brain experienced the best response to venlafaxine (Effexor).
  • People in another subtype that had a higher level of activity in three brain regions linked with depression and problem-solving experienced a better response from behavioral talk therapy.
  • People with a subtype that involves lower activity levels in the brain circuit that controls attention were less likely to see improvement with talk therapy than the other subtypes.

The study’s authors indicated that the subtypes and their response to behavioral therapy made sense based on what scientists know about the regions of the brain.

The biggest takeaway is that we can identify specific types of major depression that have a root cause in specific brain regions and networks,” said Dr. Leanne Williams, a senior author of the study.

“This discovery can be transformative,” Williams told Medical News Today. “It is a path for moving beyond diagnosis based only on observed symptoms, which is a one-size-fits all approach which doesn’t tell us which treatment will work best for each person. opens the door for precision medicine in mental health.”

The researchers suggested that the type of therapy used in the trial focused on teaching participants the skills to address daily problems, so the high activity in these regions could assist them in developing new skills.

The authors further suggested that for people with lower activity in the region associated with attention, antidepressants to increase activity before talk therapy could help.

The researchers believe that depression screening could include a brain scan to help identify the subtype and best treatment.

“It is very interesting and important to find out more about using brain activity to choose the right treatment,” said Dr. David Merrill, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in California. “Eventually, this might change how we prescribe medication, but unless you are with an educational or large hospital, you won’t have access to the fMRI scans to offer this level of diagnostics to your patients.”

“This study is more discussing the concept of choosing treatment based on brain activity,” Merrill, who was not involved in the study, told Medical News Today. “We do this to an extent in practice but asking questions about different symptoms. For example, antidepressants target different behaviors. Someone who feels tired might benefit from bupropion hydrochloride (Wellbutrin). Someone who doesn’t have much of an appetite might benefit from mirtazapine (Remeron).”

Treatment-resistant depression is when a person’s depression doesn’t respond to at least two different types of antidepressants.

About 30% of people with major depressive disorder do not respond adequately to treatment, according to a review published in 2020. The review authors also note that previous research found that only 67% of people reached remission after four trials of antidepressants and up to 20% of people with depression had symptoms for two years or longer.

For about two-thirds of people with depression, treatment fails to reverse symptoms back to healthy levels. Typically, medical professionals prescribe medications by trial and error. Although this practice is currently viewed as the best method, it can take months or years for someone to find the right drug and dose to treat their symptoms effectively.

Experts say the new study offers hope that brain imaging can help medical professionals better understand which treatment will work for a patient.

“We do currently have ways, without fMRI scans, to help when making decisions for people with treatment-resistant depression,” Merrill noted.

Pharmacogenetics is the study of genetic causes of drug responses, and pharmacokinetics looks at how medication is metabolized.

Pharmacogenetics can determine whether a medication is effective, whether a person will experience serious side effects, and the required dosage. A saliva analysis can provide genomic information.

“Often, depression is first treated at the primary care level. If a person does not respond to that treatment, they are referred to a specialist (often a psychiatrist),” said Merrill. “At that level, the physician might request laboratory tests to help with determining an appropriate treatment. If the depression still doesn’t lessen, the next step up would be a hospital or educational hospital. Laboratory tests and brain scans may be used at that level.”

“I would like to see this research continue and expand to other forms of treatment – such as cognitive behavioral therapy, electroshock therapy, ketamine treatment, and brain stimulation,” he added. “It would be interesting to see brain activity to measure the response to these types of treatment.”

Williams indicated that the team is working to improve and expand their research.

We are expanding our research to connect brain imaging biotypes to signatures that derived from digital and smartphone measures,” she said. “This approach would potentially allow for remote identification of possible biotype and flag when an individual might come for a scan. It would also allow for remote monitoring.”

“We are inspired by advances in other areas of medicine, such as in cardiology,” she added. “Patients can describe their symptoms but cannot determine the underlying brain changes. Similar to how patients with chest pain cannot know the exact heart condition without imaging, brain scans can reveal the specific brain changes linked to depression. Our studies indicate that brain scans can predict treatment responses, potentially doubling the number of patients who get better sooner. In other areas of medicine, once we know how to measure the organ involved (brain in the case of depression, the heart in the case of cardiovascular medicine), we have a basis for then connecting this deep information to other metrics, including digital.”