Parkinson's disease is a neurological disorder that typically afflicts people over 50 and is more common in men than women. Its most striking symptoms include tremor (in the hands, legs, jaw and face), stiffness, slowness and problems with balance and coordination. Parkinson's is chronic and progressive, usually starting with a subtle tremor but often progressing in a downward slide, resulting in difficulties with basic functions such as walking, talking and the physical actions of eating (swallowing and chewing). A minority of cases run in families, but most do not.
While the ultimate cause of Parkinson's disease is unknown, the proximate cause is well-described: It results from a loss of dopamine-containing cells in the brain, particularly in two regions, the substantia nigra and the ventral tegmental area -- these cells are involved not only in the initiation of movement but also comprise an essential part of the brain's pleasure circuit.
At present, there is no cure for Parkinson's disease, but a number of drug therapies are available to treat the symptoms by increasing dopamine action to compensate for the loss of dopamine-containing neurons (relief can also be found in some cases with a surgically implanted deep-brain stimulator). The first is a drug called levodopa, a chemical precursor of dopamine. When levodopa is taken up into the surviving dopamine neurons, it causes them to make more dopamine and to boost their release of dopamine. Obviously, this depends upon there being a sufficient number of surviving dopamine-making neurons -- if they are all dead, then levodopa therapy will fail. The second is a class of drug called dopamine receptor agonists. These drugs bind to dopamine receptors and activate them, thereby mimicking the actions of dopamine. Levodopa and dopamine receptor agonists are often given together, and in many cases can significantly relieve the tremor and other movement problems, providing years of symptomatic relief. Unfortunately, as Parkinson's progresses, more and more dopamine neurons die, and as a consequence these drugs have to be given at higher and higher doses to control the symptoms.
In his original 1817 description of the "shaking palsy" that came to bear his name, James Parkinson classified it as a pure movement disorder that left "the senses and intellect ... uninjured." However, that assessment has turned out not to be true and likely results from the surprising fact that Parkinson examined only a single shaking palsy patient in his medical office -- the other five cases that formed the basis of his essay were merely observed and sometimes interviewed as he walked around the streets of London. As early as 1913 it had become clear to some neurologists that Parkinson's disease also involved symptoms of cognition and mood, and that these symptoms often preceded the onset of movement disorders.1
On average, Parkinson's patients tend to be introverted, rigid, stoic, slow to anger and generally uninterested in risk-taking or seeking out novel experiences. They use alcohol, tobacco and other psychoactive drugs at a much lower rate than the general population. Their personalities and actions are, in fact, the polar opposite of typical drug addicts, who are more likely to be impulsive, quick-tempered novelty-seekers. Given that profile, it was quite unusual when case reports started appearing showing an unusually high incidence of pathological gambling among Parkinson's patients.
In January 2001, a 64-year-old man was admitted to an outpatient treatment facility for problem gamblers in northern Italy. He had lost the equivalent of $5,000 playing slot machines over a 3-year period, causing him to become estranged from his wife and to move in with his elderly mother. He had been diagnosed with Parkinson's disease 12 years earlier and had been placed on dopamine replacement therapy, consisting of a combination of levodopa and dopamine receptor agonists. The psychiatrists at the clinic performed cognitive-behavioral therapy (which is often effective for pathological gamblers) and prescribed antidepressants (serotonin-specific reuptake inhibitors, or SSRIs).
The treatment was unsuccessful, and the patient soon dropped out of the program and resumed his compulsive gambling. When he finally returned to the clinic in September 2002, the psychiatrists in charge had an insight -- they asked the patient's daughter to surreptitiously monitor her father's intake of drugs. What they found was that, acting on his own, he had significantly increased his prescribed dose of both levodopa and dopamine receptor agonists. When confronted, he readily admitted increasing the dose and stated that he enjoyed the euphoric mood that accompanied it (he liked the gambling too -- he was just concerned about losing all of his money.) When the drug doses were reduced to the prescribed level, his gambling stopped within a few days. In recent years, there have been a flood of similar case reports in the medical literature. 2
Analysis of these reports revealed an interesting finding. Among patients treated solely with levodopa, the incidence of compulsive gambling was very low (it's about 1 percent in the general population). However, among Parkinson's patients treated with dopamine receptor agonists, there was a remarkable 8 percent incidence of pathological gambling. Gambling was, in fact, only the most common manifestation of a broad range of impulse control disorders. A small but significant population of these patients started compulsively eating, shopping (or shoplifting) and having risky sex -- all behaviors that are highly atypical for the normal Parkinson's sufferer. In almost all cases, the impulse control disorder began shortly after an increase in the dose of dopamine receptor agonist and could be terminated by reducing the dose.
The best explanation for these findings is that in untreated Parkinson's disease, chronically low levels of dopamine result in a dialing down of the pleasure/reward circuit and a disinclination to seek novel experiences, and are associated with a reduced risk of addiction. In contrast, in some Parkinson's patients treated with high doses of dopamine receptor agonists, the level of dopamine action, in both the pleasure circuit and associated structures, is high, thereby dialing up the function of the pleasure circuit. This confers increased vulnerability to impulse control disorders, risky behavior and addiction.
David J. Linden is the author of a new book, The Compass of Pleasure: How Our Brains Make Fatty Foods, Orgasm, Exercise, Marijuana, Generosity, Vodka, Learning, and Gambling Feel So Good. He is a professor of neuroscience at The Johns Hopkins University School of Medicine and Chief Editor of the Journal of Neurophysiology.
1For a modern analysis of Parkinson's original report, see: Kempner PA, Hurwitz B, Lees AJ. A new look at James Parkinson's essay on the shaking palsy. Neurology 69, 482-485 (2007).
2The biomedical literature is full of reports on Parkinson's and pathological gambling. Here's one case history report I adapted: Avanzi M, Uber E, Bonfà F. Pathological gambling in two patients on dopamine replacement therapy for Parkinson's disease. Neurological Science 25, 98-101 (2004). And here's a nice review of the recent scientific literature on this topic: Voon V, Thomsen T, Miyasaki JM, de Souza M, Shafro A, Fox SH, Duff-Canning S, Lang AE, Zurowski M. Factors associated with dopaminergic drug-related pathological gambling in Parkinson's disease. Archives of Neurology 64, 212-16 (2007).