MS and depression: Could damage to the same neural circuit be a likely cause?

  • Researchers investigated the link between brain lesions from multiple sclerosis and neural circuits in the brain associated with depression.
  • They found that patients with MS and depression were more likely to have brain lesions on neural circuits linked to depression.
  • The researchers say that further studies are needed to see if brain stimulation targets useful for depression may help those with MS and depression.

In multiple sclerosis (MS), immune cells attack myelin sheaths that encase nerves, including those in the brain and spinal cord. Myelin sheaths are insulating fatty layers that enable communication between neurons.

Early symptoms of MS may include fatigue, vision problems, and numbness. Around 50% of people with MS also experience depression at some point in their life, and around 20% have the condition each year.

Understanding more about the underlying neuroanatomy for depression in those with MS could help identify treatment targets for brain stimulation techniques.

Recently, researchers used a mapping technique to understand whether brain lesions from MS are linked to neural circuits—neurons that communicate across brain regions—associated with depression. They found that MS lesions affect similar areas of the brain as depression.

“This work demonstrates that people with MS and depression are more likely to have lesions that are connected to a previously defined depression circuit in the brain,” Dr. John William Lindsey, professor, and director of the Division of Multiple Sclerosis and Neuroimmunology with McGovern Medical School at UTHealth Houston, who was not involved in the study, told Medical News Today.

“[This study] supports the idea that depression is a symptom of MS caused by MS lesions in the brain. Effective treatment of MS with therapies that slow down the disease process should also reduce depression.”
— Dr. John William Lindsey

The study was published in Nature Mental Health.

Overlap in MS, depression circuits

For the study, the researchers gathered data from 281 participants with MS from a longitudinal clinical and radiological database. Data included magnetic resonance imaging (MRI) data, self-reported depression scores, and overall disability information.

The researchers analyzed the data via a technique known as lesion network mapping. The technique works by comparing new MRI images with a pre-existing database of neural connections from 1,000 people.

In particular, they compared their new data to neural circuits already related to depression.

They found that participants with MS who had lesions in neural circuits linked to depression had higher depression scores than those with lesions elsewhere.

This relationship remained after accounting for demographic factors and fatigue, and cognitive symptoms.

The researchers further found that MS lesions linked to depression are connected to the same circuit as stroke lesions and transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) sites that modify depressive symptoms.

They noted that their data suggests that a convergent neural circuit is causally associated with depression across different conditions.

Explaining the MS, depression link

“This is an important and elegant study which builds on previous work indicating that depression in persons with MS is contributed to by structural lesions,” Dr. Barbara Giesser, neurologist and MS specialist at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California, who was not involved in the study, told MNT.

“This study confirms that lesions in the same places that are associated with depression in persons with brain damage due to other causes, such as head injury or stroke, can produce depression in persons with MS.”
— Dr. Barbara Giesser

When asked what might explain the link between depression and MS, Dr. Giesser said:

“Depression in persons with MS is most likely a combination of structural lesions, any genetic predispositions, and/or situational factors, e.g., reaction to illness. Some medications used to treat MS, notably beta-interferons, have been observed to produce depression as well.”

Depression in persons with MS should be treated in a standard fashion, e.g., with counseling/therapy, and medication as indicated.

Additionally, other issues for persons with MS which can contribute to depression, such as fatigue, pain, medication effects, or sleep disorders, should be screened for and treated.

Limitations 

The researchers noted several limitations to their findings. They noted that as their results were based on a single depression score, they may not capture the full breadth of clinical representations.

They further noted that they did not their findings do not account for pharmacological interventions such as antidepressants.

What this means for MS patients

Although the results could offer scientists a target for brain stimulation, further work is needed before this becomes a wide-held practice.

“The article states that depression caused by structural damage due to other causes, such as head injury or stroke, has been demonstrated to respond to targeted brain stimulation. This technique might also be useful in treating depression in persons with MS but further study is needed,” Dr. Giesser said.

“This technique requires sophisticated imaging and processing and will be difficult to transfer to clinical practice. There is not a single area or group of areas in the brain that cause depression, but rather an extensive, interconnected circuit,” pointed out Dr. Lindsey.

“The authors suggest a trial of transcranial magnetic stimulation for MS depression which is an interesting suggestion,” he added.

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