Researchers Discover Intriguing Link Between Epilepsy and Depression

Researchers have noted a higher incidence of depression among patients with epilepsy than the general population or others with chronic conditions such as diabetes. For a long time, depression was thought to be a complication of epilepsy.

But there is evidence that the connection between epilepsy and depression may be a two-way street, according to research carried out in Sweden and the United States that will be reviewed at AAAS's annual meeting in Washington, D.C.

"People with a history of depression have a 3 to 7 times higher risk of developing epilepsy," said Dr. Andres Kanner, a specialist on epilepsy at Rush University Medical Center in Chicago. "This kind of information is forcing us to take a second look at the interaction between depression and epilepsy."

Since depression affects about 5.3 percent of the U.S. population and epilepsy about 0.5 to 1 percent, session organizers said, knowledge of any relationships between the two disorders could help physicians find ways to improve care for both groups. The two-way relationship between epilepsy and depression could mean common pathogenic mechanisms are at work, Kanner said.

Studies with rats that are genetically prone to epilepsy show abnormal secretion in the brain of neurotransmitters such as serotonin, norepinephrine, GABA and dopamine. The abnormal secretion patterns of serotonin and norepinephrine in these animals are similar to abnormal patterns for the same neurotransmitters seen in patients with depression, Kanner said. He summarized the evidence for common biological pathways in a paper published in January in the journal Epilepsy Currents. Phillip C. Jobe of the University of Illinois College of Medicine, another speaker at the meeting, also has studied underlying biological factors that may predispose some people to epilepsy and depression.

Common pathways between depression and epilepsy might account for recent data suggesting that patients with a psychiatric history may not respond as well to medication or surgery for treatment of their seizures, Kanner said. He and his colleagues recently studied 90 patients whose seizures failed to respond to antiepileptic medication and underwent brain surgery to remove tissue that was the focus of the seizures. Patients with a lifetime history of depression were less likely to become seizure-free, the researchers found. Kanner said that suggests depression could be a biological marker for a more severe form of epilepsy.

Epilepsy, marked by unprovoked seizures, is caused by recurrent electrical "storms" in the brain. More than 2.5 million Americans of all ages are living with epilepsy, which can develop at any time of life but especially in early childhood and old age, according to the Epilepsy Foundation.

Possible links between depression and epilepsy have been noted since around 400 B.C., when Hippocrates, the Greek physician, reportedly observed, "Melancholics ordinarily become epileptics and epileptics melancholics." Galen, another Greek physician, later wrote a treatise titled "Epilepsy and Melancholy."

Whatever biological links the two disorders may share, clinicians and patients alike need to be more aware of the significant incidence of depression among those with epilepsy, says Dr. Alan Ettinger of the Long Island Jewish Comprehensive Epilepsy Center. That is true, he said, even of patients who exhibit less severe forms of the condition than those treated at specialized clinics and major medical centers.

Ettinger and his colleagues surveyed 775 epilepsy patients in community settings, 395 asthma patients and 362 healthy control subjects. Among those with epilepsy, 36.5 percent reported symptoms of depression, compared to 27.8 percent of asthmatics and 11.8 percent of controls. The study, published in the journal Neurology in September, also found that nearly 39 percent of the patients with epilepsy had never been evaluated for depression. Ettinger said it is important for doctors and patients to understand that those with epilepsy, even mild forms of the condition, face an elevated risk of depression.

— Earl Lane

18 February 2005