This basal ganglia (striatum) is one of my favorite research areas. I am so glad that the research in this area is continuing...
Biol Psychiatry. 2016 Feb 15;79(4):320-8. doi: 10.1016/j.biopsych.2015.05.015. Epub 2015 Jun 4.Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue. Dowell NG1, Cooper EA2, Tibble J3, Voon V4, Critchley HD5, Cercignani M6, Harrison NA7.
We know that hepatitis C patients receiving IFN-a and ME/CFS patients have very similar problems with fatigue and identical problems in the basal ganglia. That by itself is really interesting. It's not people with hep C infections who are similar to ME/CFS patients it's hep C patients receiving a major immune booster - IFN-a - that do. That suggests that immune activation is whacking both ME/CFS and hep C patients with IFN-a.
[fright]
[/fright]This review focused somewhat depression but I would discard that term and just call it "sickness behavior". (The understanding that IFN-a administration in hep C patients caused fatigue, depression, etc. helped researchers understand that the immune system - not the infection - was largely responsible for the flu-like symptoms we experience when we have a cold.
Miller has found that reduced activation of the reward system in the basal ganglia in both hep C patients on IFN-a and ME/CFS was highly associated with fatigue. He believes that reduced dopamine levels in the BG result in an increased sensitivity to inflammation.
Now comes this study which directly shows what happens in the brain when an inflammatory mediator like IFN-a is added. It found that microstructural changes in the striatum in the brain (a part of the BG) began to occur within hours of the IFN-a injection. The more changes seen in the striatum early on the more fatigue the patients experienced later on.
This could very be a model for what happens in ME/CFS patients during triggering infections. We know that people who come down with a post-infectious illness produce more cytokines early in an infection. What we don't know is why they remain sick. Changes to the striatum very early on in the infection could help explain why.
The study also found that changes in the striatum could also help explain why some people with ME/CFS get fatigued and depressed while others only become fatigued. Different circuits in the striatum seem to predispose for fatigue while others predispose for depression. If both circuits in your striatum got whacked you got the full monty - fatigue plus depression. If only the fatigue circuit got whacked you got something like ME/CFS and if only the depression circuit got whacked you just became depressed.
Biol Psychiatry. 2016 Feb 15;79(4):320-8. doi: 10.1016/j.biopsych.2015.05.015. Epub 2015 Jun 4.Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue. Dowell NG1, Cooper EA2, Tibble J3, Voon V4, Critchley HD5, Cercignani M6, Harrison NA7.
We know that hepatitis C patients receiving IFN-a and ME/CFS patients have very similar problems with fatigue and identical problems in the basal ganglia. That by itself is really interesting. It's not people with hep C infections who are similar to ME/CFS patients it's hep C patients receiving a major immune booster - IFN-a - that do. That suggests that immune activation is whacking both ME/CFS and hep C patients with IFN-a.
[fright]
Miller has found that reduced activation of the reward system in the basal ganglia in both hep C patients on IFN-a and ME/CFS was highly associated with fatigue. He believes that reduced dopamine levels in the BG result in an increased sensitivity to inflammation.
Now comes this study which directly shows what happens in the brain when an inflammatory mediator like IFN-a is added. It found that microstructural changes in the striatum in the brain (a part of the BG) began to occur within hours of the IFN-a injection. The more changes seen in the striatum early on the more fatigue the patients experienced later on.
This could very be a model for what happens in ME/CFS patients during triggering infections. We know that people who come down with a post-infectious illness produce more cytokines early in an infection. What we don't know is why they remain sick. Changes to the striatum very early on in the infection could help explain why.
The study also found that changes in the striatum could also help explain why some people with ME/CFS get fatigued and depressed while others only become fatigued. Different circuits in the striatum seem to predispose for fatigue while others predispose for depression. If both circuits in your striatum got whacked you got the full monty - fatigue plus depression. If only the fatigue circuit got whacked you got something like ME/CFS and if only the depression circuit got whacked you just became depressed.
Press Release: Elsevier, February 2, 2016. A new study by Neil Harrison and colleagues published in Biological Psychiatry suggests that a brain reward center, the striatum, may be directly affected by inflammation and that striatal change is related to the emergence of illness behaviors.
Inflammation increases the risk for depression. More specifically, inflammation induces behavioral changes similar to depression that are often associated with illness, including fatigue, difficulty concentrating, lack of motivation, and reduced experience of pleasure.
The authors recruited 23 patients with hepatitis C who were beginning treatment with interferon-alpha (INF-α). This treatment provokes an immediate inflammatory response, confirmed by measuring cytokines in the blood.
Four hours after INF-α administration, a specialized type of imaging, called magnetization transfer imaging, was performed that showed evidence of microstructural changes in the striatum when compared to scans conducted prior to INF-α administration. This suggests that the striatum is highly sensitive to IFN-α.
IFN-α also induced fatigue and depression in the patients, particularly over weeks 4 through 12 of treatment. Interestingly, the early striatal structural change predicted the later emergence of fatigue, but not depression, in the study participants.
Changes in the striatum were heterogeneous with some changes associated with the risk for fatigue, while other changes seemed to be protective against developing fatigue.
"Inflammation-related fatigue and depression are big clinical problems," said Dr. John Krystal, Editor of Biological Psychiatry. "This study highlights that the brain regions central to reward and motivation are directly altered by inflammation in ways that that appear to predispose or protect against developing fatigue but not depression. The heterogeneous striatal response may suggest that fatigue and mood are supported by different microcircuits within the striatum."
"These findings are important as they show that a relatively simple MRI technique can be used to measure effects of inflammation on the brain," Harrison commented. "Inflammation is increasingly implicated in the cause of common mental illnesses, particularly depression. This technique could be a powerful way to identify patients who are most sensitive to effects of inflammation on the brain. It could also be used to monitor response to novel anti-inflammatory therapies that are now being tested in depression."
Journal Reference: Nicholas G. Dowell, Ella A. Cooper, Jeremy Tibble, Valerie Voon, Hugo D. Critchley, Mara Cercignani, Neil A. Harrison. Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue. Biological Psychiatry, 2016; 79 (4): 320 DOI:10.1016/j.biopsych.2015.05.015