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DEPRESSION AND PARKINSON'S DISEASE page 1 of 2 If you are a rat, and obtain something that you want, such as a bit of candy or a drink of water, you experience a feeling of pleasure. Over several decades, researchers have known this phenomenon as the "reward system". Rats can be trained to work for the rewarding pleasure, by pressing a lever, running a maze, etc. Furthermore, stimulation of a certain part of the brain by an implanted electrode evokes pleasure just as effectively as real candy or water, and rats can be trained to work for that. The electrical stimulation has the advantage that it can be varied, to see just how badly the rats crave it, or how hard they will work for it. Researchers use the reward to study substance addiction. For example rats, accustomed to getting nicotine and then deprived of it, worked until the stimulation intensity reached a certain value known as the threshold value, that measured the degree of addiction. Over the years, workers have also learned that a major component of the brain reward system is a small group of nerve cells that project from the deep midbrain to a ventral forebrain region called the nucleus accumbens, and that use dopamine as their chemical messenger. Enhanced dopamine transmission in this system seems to be intricately involved with the sensation of pleasure, so it is sometimes called "the reward pathway". And by analogy, a similar pleasure pathway is thought to exist in people. Recently, workers have found a way to observe the relation of dopamine to the reward pathway in human subjects. Using positron emission tomography (PET) scan imaging, and a tracer that is displaced from receptors by dopamine, they could map the release of dopamine as a function of the subject's behavior. The volunteers played a video game while being scanned, and were offered additional money as a bonus for "winning" the game. The pleasure of earning the prize was thus correlated to the release of dopamine. Note, while PWP have always known that dopamine affects behavior, this is the first observation of the converse, that behavior affects dopamine. Might the causes of PD possibly include a behavioral factor? Now, a very common secondary symptom of PD is clinical depression, usually assessed by means of a psychological questionnaire. And the clinical depression that afflicts many times more people than those with PD is known to arise from a deficit in another neurotransmitter, serotonin. That form of depression is one of the most easily managed neurological diseases, and millions of people take serotonin-enhancing drugs such as Prozac, Zoloft, Paxil, Norpramine, etc, for effective relief. But do such drugs always work as well for depression in PWP? My hypothesis is this: Depression = Lack Of Pleasure = (sometimes) Lack Of Dopamine. DEPRESSION AND PARKINSON'S DISEASE page 2 of 2 I believe there are many PWP who take dopamine-enhancing drugs (such as Sinemet) periodically, and who experience depression near the conclusion of the dosage interval as a "wearing-off" effect. Those same people, I expect, also get an emotional lift immediately following the dose of PD medication, as a "peak-dose" effect. Therefore, I propose that there are two different sources of chemical-related depression, not necessarily exclusive: One is the deficiency of serotonin, as discussed above. The other is the deficiency of dopamine, well known as the cause of motor symptoms in PD, and here implied also to exist independently in the so-called reward or pleasure pathway. I and some other PWP call this alternating state "mood swings" because they arise only from changes in the supply of available dopamine, and they respond to dopamine-enhancing medication. Could it be that the neural degeneration of PD sometimes extends to the reward pathway as well as the motor control centers? If my suspicion is right, a PWP might have one kind of depression but not the other; or both together; or neither one. The notion might be verified eventually by collecting a body of data from postmortem examination of "depressed" PD patients. Bottom Line, for People With Parkinson's Plus Depression: If Prozac doesn't work for you, maybe all you need is a bit more of your usual PD medication. Ask your doctor. Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013