Anxiety in Epilepsy Linked to Volumetric Brain Changes

Kate Johnson

July 03, 2013

MONTREAL — Children with concurrent epilepsy and anxiety have volumetric brain changes similar to those observed in nonepileptic patients with anxiety, new research shows.

"Frequently, anxiety in epilepsy is viewed as a result of the unpredictability of seizures and is not treated," Jana Jones, PhD, assistant professor in neuropsychology at the University of Wisconsin School of Medicine and Public Health in Madison, told Medscape Medical News.

"But the results of this study suggest that there is a presence of an abnormal underlying neural biology that may be affecting some subcortical and cortical regions implicated in anxiety.

"The clinical implication of this finding is that evidenced-based treatments for anxiety disorders should be utilized in children with epilepsy and anxiety, particularly if the neurobiology is similar in individuals with anxiety regardless of seizure status."

The findings were presented here at the 30th International Epilepsy Congress (IEC).

Multiple Anxiety Disorders

The study included 88 children with epilepsy (24 with concurrent anxiety and 64 without) and 50 control participants without epilepsy or anxiety who were first-degree cousins of the epilepsy patients.

The median age of participants was 12.8 years (epilepsy alone), 12.1 years (epilepsy plus anxiety), and 13.3 years (control individuals).

Age at seizure onset and duration of epilepsy was 12.1 years and 7.9 months, respectively, in participants with anxiety, and 11.2 years and 8.5 months in participants without.

"Children with epilepsy were assessed within 12 months of their diagnosis, had normal neurological exams and normal clinical MRI [magnetic resonance imagining]," said Dr. Jones.

All participants and their parents completed a semistructured psychiatric interview (Kiddie Schedule for Affective Disorders and Schizophrenia).

In terms of types of anxiety disorders that were identified, "the most frequent diagnosis was specific phobia, and then second was separation anxiety, followed by social phobia and generalized anxiety disorder," she said. "Many of the children had more than 1 anxiety disorder, or a depressive disorder was also present."

Participants also underwent T1 MRI brain scans.

"We focused on amygdala volumes and the prefrontal cortex thicknesses related to hypotheses from the general literature that we know about anxiety disorders and their involvement in these brain regions," said Dr. Jones.

"These brain regions have not really been examined in kids with new or recent-onset epilepsy who also have a current anxiety disorder."

Identify, Treat Anxiety

The study showed that children with anxiety disorder plus epilepsy had significantly larger left amygdala volumes compared with children with epilepsy alone as well as control individuals.

"In children with epilepsy plus anxiety, both the left and right amygdala volumes were greater — but only significantly so in the left amygdala," she noted. Significance for each comparison was set at a P-value of 0.05 or less.

Similarly, children with epilepsy and anxiety showed a pattern of cortical thinning in frontal lobe regions known to be associated with emotion and anxiety in the general population, she said.

Specifically, the medial orbital prefrontal cortex was thinner in children with epilepsy plus anxiety compared with those with epilepsy alone and control participants. Again, this was true for both the left and the right side, but only significantly so on the left.

In contrast, volumetric analyses in control regions of the hippocampus and precentral gyrus showed no differences between control individuals, patients with epilepsy alone, and those with epilepsy plus anxiety.

"Both the amygdala and prefrontal cortex have been implicated in anxiety in the general population," noted Dr. Janis. "They appear to work closely together to interpret anxiety and fear and determine a response. The amygdala is part of the limbic system and mediates the effects of emotional arousal. It also known as the fear center. The prefrontal cortex appears to modulate the expression of anxiety, fear, and stress."

She said that her findings point to the importance of diagnosing and treating anxiety in children with epilepsy.

"We know that untreated anxiety in childhood increases the likelihood of depression and other comorbid psychiatric conditions in adulthood, so it is important to treat these conditions early," she said, adding that her group recently conducted a pilot study using cognitive-behavioral therapy to which children responded "quite well."

Important Study

Commenting on the findings for Medscape Medical News, Karen Blackmon, PhD, said it is "an important study in that it demonstrates a primary neurobiological component to anxiety in epilepsy, not just a secondary emotional reaction to living with the burden of seizures."

"Evidence for abnormalities in this network, as demonstrated in the current study, suggests that the ability to dampen down a fear response may be compromised in a subset of children with epilepsy. This knowledge can be used to direct therapeutic goals such as developing compensatory strategies for regulating fear that might utilize other regions of the brain," added Dr. Blackmon, who is assistant professor in neurology at New York University Langone Medical Center in New York City.

Dr. Blackmon further added that amygdala enlargement has previously been documented in childhood epilepsy with anxiety ( Epilepsy Behav 2009;16:436-41). However, she said, what is new about this study is the finding of prefrontal thinning.

"If there is pathology or decreased network efficiency in the prefrontal lobes of children with epilepsy, this may increase their vulnerability to anxiety in that they are compromised in their ability to downregulate a fear response. Ideally, future work should test whether there may be abnormal connectivity between the prefrontal and amygdala region in patients with epilepsy and anxiety, considering these structures as part of a network, rather than in isolation," said Dr. Blackmon.

The study was funded by the US National Institutes of Health.

30th International Epilepsy Congress. Abstract 037. Presented June 25, 2013.


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