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Depression, Epilepsy Link Puzzles Researchers

New research suggests that depression, suicide, and epilepsy may all be common, yet distinct, bedfellows.

Researchers at Columbia University and the University of Reykjavik, Iceland, have identified a potential link between depression, suicide, and epilepsy. Epilepsy, they believe, is linked to both depression and suicide, but the link is probably through different brain mechanisms. Surprisingly, however, they found no statistically significant link between suicide and depression.

The report, supported by the National Institute of Neurological Disorders and Stroke, was published online in advance of print in the "Early View" section of the Annals of Neurology.

"For reasons that are not understood, depression both increases the risk for developing epilepsy and is also common among people with epilepsy who experience many seizures," said lead author Dale Hesdorffer, Ph.D., in a press release. Hesdorffer is an assistant professor of epidemiology at the Gertrude Sergievsky Center at Columbia University.

The report noted that "it has commonly been assumed that the difficulties associated with living with epilepsy could provoke depression and, in some cases, an increased risk of suicide. But it is harder to explain the opposite finding—that people who develop depression have a higher risk of later experiencing a first seizure."

Over the last decade, neuroscientists have hypothesized that depression and epilepsy may involve overlapping brain systems, but evidence for a dual mechanism is preliminary. Hesdorffer and his colleagues hoped to define more clearly the relationship between depression, suicide, and epilepsy.

"One question we had was whether some symptoms of depression were more important than others for increasing the risk for developing epilepsy," said Hesdorffer. "Suicidal thoughts and suicide attempt were possibilities, because people with epilepsy seem to be more likely to commit suicide than the general population. But we looked at all symptoms of depression."

Hesdorffer and colleagues undertook a population-based case-control study of 324 Icelandic children and adults (aged 10 and over) who had a new diagnosis of unprovoked seizures or epilepsy between December 1, 1995, and February 28, 1999, and 647 control subjects without epilepsy.

The researchers expectedly found that a history of depression increased the risk of epilepsy (odds ratio 1.7 compared with controls). However, the team was surprised to find that people with epilepsy were 3.9 times more likely than controls to have attempted suicide before ever having a seizure. The elevated risk remained strong (odds ratio 3.5 compared with controls) even after other factors were taken into account like alcohol consumption, history of depression, age, and gender.

The individual presence of symptoms that did not meet threshold criteria for major depressive disorder did not predict a greater likelihood of later development of seizures.

Those with a history of depression and a previous suicide attempt were 13.3 times more likely than controls to develop seizures. Subjects with a history of suicide attempt but not depression were 4.2 times more likely than controls to develop seizures. Subjects with a history of depression but not suicide attempt were 1.5 times more likely to develop seizures in the future; however, this finding did not reach statistical significance.

The researchers reported that the results suggest common underlying brain mechanisms for suicidal behavior and epilepsy. Yet, they added, the results also suggest that depression and suicidal behavior may be related to different mechanisms.

"Increasingly, clinicians treating people with epilepsy ask about current depression, but they may not ask about past suicide attempt or suicidal thoughts," said Hesdorffer. "Our results may alert clinicians to the need to ask this question and offer any needed counseling to prevent the occurrence of later completed suicide."

"We plan to follow up with studies designed to see whether the co-occurrence of these disorders is explained by shared genetic susceptibility and with studies that examine possible common underlying neurotransmitter abnormalities," said Hesdorffer.

An abstract of "Depression and Suicide Attempt as Risk Factors for Incident Unprovoked Seizures" is posted at <www3.interscience.wiley.com/cgi-bin/abstract/112100865/ABSTRACT>.

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