Neuropsychiatric Symptoms of Epilepsy

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M. Beghi et al.
Depression itself and antidepressants have been examined as risk factors for
developing epilepsy. Individuals with a history of major depression and/or suicide
attempts are at increased risk for developing new-onset epilepsy [ 16 – 19 ], raising the
possibility that depression and epilepsy share a common pathophysiology. Further
evidence for this hypothesis can be found in studies showing that current neuropsychiatric
disability and depression are associated with a worse seizure outcome in
people with new-onset epilepsy and that a lifetime history of psychiatric disorders,
and more specifically of depression, is associated with a worse seizure outcome
after anterior temporal lobectomy [ 20 ]. Epilepsy and depression share an unusually
high co-occurrence leading to a common etiology. Disrupted production of adultborn
hippocampal granule cells in both disorders may contribute to this high cooccurrence
[ 21 ]. Chronic stress and depression are associated with decreased
granule cell neurogenesis [ 21 ]. Epilepsy is associated with increased production
and aberrant integration of new cells early in the disease and decreased production
of new cells late in the disease [ 21 ]. In both cases, these changes in neurogenesis
play important roles. Aberrant integration of adult-generated cells during the development
of epilepsy may impair the ability of the dentate gyrus to prevent excess
excitatory activity from reaching hippocampal pyramidal cells, which promote seizures
[ 17 ]. Moreover, studies in mice underline that lack of exercise, very common
in depressed patients, causes a reduction in galanine production, with consequent
increase in seizure frequency [ 22 ].
The mechanism leading to seizures in these individuals may thus be correlated
with the pathophysiology of depression, suggesting different treatment strategies.
The treatment of depression can improve seizure frequency. In placebo-controlled
studies of serotonine selective reuptake inhibitors (SSRIs) or serotonine and norepinephrine
reuptake inhibitors (SNRIs) for treating depression, those treated with a
drug showed a 50 % reduction in the occurrence of seizures as adverse events, and
those on placebo experienced a 19-fold increased risk for developing seizures compared
to the general population [ 20 ]. These findings may imply serotonergic mechanisms
underlying the observed comorbidity [ 20 ].
Bipolar Disorder and Epilepsy
Although mood disorders represent a frequent psychiatric comorbidity among
patients with epilepsy, data regarding bipolar disorders are still limited. Recent data
suggest that mood instability is actually frequent among patients with epilepsy but
is phenomenologically different from that described in bipolar disorders [ 23 ].
Epilepsy and bipolar disorders are both episodic conditions that can later become
chronic. Mania may represent a privileged window into the neurobiology of mood
regulation and the neurobiology of epilepsy itself [ 23 ]. The kindling paradigm,
invoked as a model for understanding seizure disorders, has also been applied to the
episodic nature of bipolar disorders [ 24 ]. These two conditions apparently share a
number of biochemical and pathophysiological underpinnings. Common