Neuropsychiatric Symptoms of Epilepsy

1 Neurobehavioral Comorbidities of Epilepsy: Lessons from Animal Models
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attention, social interaction, all have been reported within the framework of a single
epilepsy model. The problem therefore is not a system-limitation proper, but the fact
that typical experimental design simply ignores multiple neurobehavioral impairments
in favor of a single disorder, which is the primary focus of the project.
Not only such simplification overlooks the complexity of real life, but it also can
lead to faulty interpretations. Indeed, similar to clinical situations, in laboratory
systems, coexisting neurobehavioral comorbidities may influence one another, and
therefore may skew outcome measures (e.g., the presence of anxiety will likely
affect the way epileptic animal performs in cognitive tasks, and the presence of
depressive disorder – performance in attention tasks; Fig. 1.7 ).
ADHD
Anxiety
Cognitive
impairments
Depression
Fig. 1.7 Multiple interactions between seizures and neurobehavioral disorders in animal models
of epilepsy comorbidities. Epilepsy proper (including both recurrent seizures and interictal events,
such as interictal spikes) affects animal’s behaviors and hence the performance in respective tests
(examples given are lateralized reaction time task for ADHD, Morris water maze for spatial cognitive
deficits, the forced swimming test for depression, and the elevated plus maze test for general
anxiety). Furthermore, seizure–behavior interaction is often bidirectional (e.g., depressionassociated
suppression of serotonergic transmission or ADHD-associated compromised noradrenergic
transmission may further exacerbate epilepsy). In addition, concurrent neurobehavioral
disorders in animals with epilepsy interact with each other and thus may influence outcome measures.
For example, the presence of depressive impairments may affect animal’s performance in
cognitive and memory tasks; the presence of ADHD may affect animal’s ability to perform adequately
in tests for depression, anxiety, etc. Such interactions emphasize the complexity of experimental
animal systems and call for a systemic, rather than isolated, approach for studying
neurobehavioral comorbidities of epilepsy in the laboratory