When a Drug Leads to Suspicions of Infidelity


by Tom Valeo

October 9, 2012

Othello syndrome —the delusional belief that one’s partner is having sexual relations with someone else —has long been recognized as a product of brain damage. A stroke, a tumor, or some other injury, especially to the right frontal lobe, may produce delusional jealousy so intense that it leads to violence or divorce.

Now, however, it appears that the syndrome may also result from medication intended to restore fluent movement to people with Parkinson’s disease, whose muscles have become slow and rigid because a region of their brain known as the substantia nigra has stopped producing sufficient levels of the neurotransmitter dopamine. In rare cases the treatment, which attempts to boost dopamine levels, brings on this stubborn delusion, which can transform a previously trusting relationship into a nightmare of suspicion, bitterness, and relentless accusations of infidelity.

The sheer strangeness of Othello syndrome aroused the curiosity of Keith Josephs, a professor of neurology at the Mayo Clinic College of Medicine in Rochester, Minn.

“I think of Othello syndrome as a delusion —an abnormal thought, sort of like believing in aliens,” said Josephs, winner of the 2009 Judson Daland Prize for outstanding achievement in patient-oriented research. “It’s as though a man decides, 'My wife is having an affair, and no one is going to talk me out of believing that.'”

As an illustration, Josephs describes a 42-year-old man with Parkinson’s disease who started to demand frequent sex from his wife while he was taking pramipexole, a drug that binds to dopamine receptors and mimics the action of dopamine. The man also was taking a combination of carbidopa and levodopa, which work together to boost levels of dopamine in the brain.

Under the influence of these drugs, the man started to accuse his wife of having an affair. He obsessively watched the driveway because he expected to find a car parked there, waiting to pick up his wife so she could go off and have sex. He also lost $3,000 while trying to satisfy a sudden urge to gamble, and came home one day with two new fishing poles even though he already owned five.

The man was a bundle of impulse control disorders, a recognized side-effect of dopamine agonists given to Parkinson’s patients to boost their inadequate levels of dopamine, but Josephs had never seen the drugs produce such an intense belief in a spouse’s infidelity.

“Then I saw a second patient,” he said. “I reviewed the literature and came across Othello syndrome, which described my patient. I thought, if I have seen two patients with this, and everyone else sees two, no one would ever notice the connection, but when you pull 100 patients together into one study, you really have some valuable data.”

By drawing on electronic records available at the Mayo Clinic, Josephs assembled information on 105 cases of Othello syndrome for a study he and his colleagues recently published in the European Journal of Neurology.

They found that 73 of the patients with Othello syndrome had an overt neurological disorder such as Lewy body dementia, a tumor, or a stroke, usually involving the right frontal lobe; the remaining 32 had psychiatric disorders such as delusions, depression, or schizophrenia.

The data supported what has long been assumed —that Othello syndrome emerges from neurological disorders that frequently produce dysfunction in the right frontal lobe.

“Damage to the right frontal lobe seems to be associated with lot of unusual and strange behaviors,” Josephs said. “There’s something unique about the right frontal and the right temporal lobes. When connections between them are disrupted, you see these strange delusions and behaviors.”

People who develop Capgras syndrome, for example, which usually emerges after damage to the right frontal lobe, start to believe that those who normally arouse intense feelings —parents, their spouse, good friends —are actually imposters. In his book, The Tell-Tale Brain, V.S. Ramachandran, a neuroscientist at the University of California, San Diego, proposes that people with Capgras syndrome have suffered a disruption of the connections between the visual areas needed to see people and the limbic structures in the temporal lobe that provide the “emotional jolt” that the sight of intimates normally produces. “The brain abhors internal anomalies —such as the mismatch between emotion and identification in Capgras syndrome —and will often go to absurd lengths to deny them or explain them away,” Ramachandran writes.

Dysfunction in the right frontal lobe may explain how a neurological problem can produce an apparent psychiatric problem such as Othello syndrome, according to Richard Camicioli, a clinical neurologist in the department of medicine at the University of Alberta. In a paper titled, “Othello syndrome —at the interface of neurology and psychiatry,” published last year in Nature Reviews Neurology, Camicioli examined the available literature and proposed that loss of function in the right hemisphere weakens the inhibition normally exerted by that part of the brain.

The left hemisphere generates interpretations of experience that help us make sense of our experience, Camicioli said. The right hemisphere —especially the right frontal lobe —helps us to monitor our actions and detect anomalies. This brain region performs the function of a fact checker, monitoring the interpretations of the left hemisphere for plausibility and accuracy. When the right hemisphere is damaged, the left hemisphere is free to issue interpretations that might make no sense.

“The brain doesn’t have a little man in the right and left hemispheres,” Camicioli said. “The brain works as a unit, but the hemispheres specialize in different things. When an imbalance develops —when one hemisphere becomes less active —you get over-activation in the other hemisphere. Disrupting the marriage between the two hemispheres leads to discord.”

A surge of dopaminergic activity, whether produced by cocaine, methamphetamine, pramipexole, or some other substance that affects dopamine levels, can produce impulse-control problems such as compulsive gambling and hypersexuality, as well as overt delusions such as the suspicions of infidelity seen in Othello syndrome. How dopamine does this remains obscure, but Camicioli suspects an imbalance in dopamine activity.

“Dopamine is involved in our reward system, and can drive our behavior,” he said. “With Parkinson’s disease, you have a loss of dopaminergic transmission in one part of the brain, but other parts don’t have as much damage, so if you take a dopamine agonist you may get an excess of dopamine in some brain regions, and develop impulse control problems or delusions.”

Since dopamine is so active in the brain, and so susceptible to modulation, might the delusions and impulse-control problems seen in people who take drugs for Parkinson’s disease be seen, in a milder form, by people espousing implausible beliefs, such as alien visitation?

“Sure, absolutely,” Josephs said. “No doubt about that.”