Breaking News: A Novel Role for Dopamine
For years, I’ve been engrossed in studying the relationship between the body, movement, and emotionally mediated illnesses like anxiety, depression, chronic pain, and PTSD.
If you’d like a little background: In this article, I shared my conviction that loss of proprioception is not just a side effect but a major driver of depression. And this one explored the role of body agency in depression.
Today, I’m going to tie these threads together through a groundbreaking new study that links movement, Parkinson’s Disease, and dopamine, and its implications for depression.
Parkinson’s Disease is neurodegenerative disease characterized by disordered movement, gastrointestinal illness, and profound depression. (You can read more on the gut in Parkinson’s here.)
Parkinson’s is caused by the degeneration of nerve cells in the part of the brain called the substantia nigra, which controls movement. When these nerve cells become impaired, they lose the ability to produce dopamine, an important brain chemical that regulates our motivation and reward systems.
Parkinson’s and Movement
For decades, researchers have been confounded by a mystery: Why do patients with Parkinson’s Disease lose dopamine neurons, yet have difficulties with movement? (Hold that thought: In a few moments, I’ll explain what that has to do with depression.)
A key feature of Parkinson’s Disease is bradykinesia, which involves a slowness of movement also seen in depression, plus a hesitation or halting of movement and difficulty with balance and coordination. The disease also features irregularities in dopamine, including motivation and reward—which are also compromised in depression.
But that’s not all: people with Parkinson’s Disease also have difficulty with internally generated movements, ones that are initiated in the absence of external cues. This refers to the fact that movements cued by one’s own intrinsic agency are more vulnerable than movements primed by external factors.
This indicates a loss of the sense of agency in Parkinson’s Disease.
This is yet another feature that Parkinson’s shares with depression. People with depression experience a lack of agency, the sense that they can have an intention and empower their bodies to achieve it. And like those with Parkinson’s, they have a scarcity of internally generated movement.
That’s the background; now on to the study.
Expanding the View of Dopamine
Dopamine is a neuromodulator, a type of neurotransmitter that affects the behavior of other neurotransmitters. In popular culture, there exists a longstanding assumption that most dopamine neurons respond to reward-related cues. Recently, that assumption has expanded to include motivation as well.
In the study, which was published in early August of 2023 in the prestigious journal Nature, two thirds of the dopamine neurons responded with avoidant behavior (to aversive stimuli) or approach behavior (to rewards). But what about the other third?
Researchers discovered a new specific subtype of dopamine neuron located exactly where neurons first begin to degrade in Parkinson’s Disease. What’s more, this neuron subtype does not become active in response to reward or motivation, but when the body moves.
This is huge news.
Dopamine controls not just reward and motivation, but movement. This explains why Parkinson’s Disease involves the loss of dopamine neurons and depression, yet also impacts the body’s movement.
In an interview with Northwestern University’s online news magazine, co-author Daniel Dombeck said,
“It’s not like people with Parkinson’s Disease only lose their drive to be happy because their dopamine response is damaged. Something else is going on that affects motor skills.”
To my reading, the author here relates happiness (or depression) not just to reward and motivation, but directly to movement.
Dombeck’s words directly link the depression that people with Parkinson’s contend with to the loss of movement they experience.
Dopamine has also long been implicated in depression. And depression compromises the reward system, motivation, and movement.
The researchers noted that the neurons that tend to die in Parkinson’s correlate with acceleration; the ones that survive regulate deceleration, or lack of movement.
Dombeck and colleagues wonder whether it’s not just loss of the movement-initiating signal that contributes to the disease, but preservation of the movement-inhibiting signal in addition. And we also know that there’s some movement inhibition in depression.
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Ultimately, this hints at a more nuanced understanding of treatments for depression. It helps the field move from the “just add exercise” prescription to the potential for priming the type of movement lost in depression.
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And just a final thought: In this Masterclass on ADHD, I teach about the hypoactivity in dopamine neurons in ADHD. So this makes me wonder whether in ADHD, the specific neurons impacted are the ones that involve not movement or reward, but inhibition. I’m planning to stay tuned to that thread.
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Sources:
People with Parkinson’s have difficulty with internally generated movements: Hess, C. W., & Hallett, M. (2017). The Phenomenology of Parkinson's Disease. Seminars in neurology, 37(2), 109–117. https://doi.org/10.1055/s-0037-1601869
In the study, which was published in early August in the prestigious journal Nature: Azcorra, M., Gaertner, Z., Davidson, C., He, Q., Kim, H., Nagappan, S., Hayes, C. K., Ramakrishnan, C., Fenno, L., Kim, Y. S., Deisseroth, K., Longnecker, R., Awatramani, R., & Dombeck, D. A. (2023). Unique functional responses differentially map onto genetic subtypes of dopamine neurons. Nature neuroscience, 10.1038/s41593-023-01401-9. Advance online publication. https://doi.org/10.1038/s41593-023-01401-9
Dopamine has also long been implicated in depression: Belujon, P., & Grace, A. A. (2017). Dopamine System Dysregulation in Major Depressive Disorders. The international journal of neuropsychopharmacology, 20(12), 1036–1046. https://doi.org/10.1093/ijnp/pyx056