A noradrenergic and serotonergic hypothesis of the linkage between epilepsy and affective disorders

Noradrenergic and/or serotonergic deficits, as well as other abnormalities, may contribute to predisposition to some epilepsies and depressions. Evide nce for this hypothesis stems from several sources. Epidemiological investi gations are intriguing but incomplete. Pharmacological studies show that no radrenergic and/or serotonergic transmission are both anticonvulsant and an tidepressant. Therapeutically pertinent investigations show that antidepres sant drugs have anticonvulsant properties, whereas antiepileptic drugs are effective in the management of affective disorders. Additional investigatio ns demonstrate that seizures, whether spontaneously occurring or therapeuti cally induced, protect against depression. Through studies of innate pathop hysiology, noradrenergic and serotonergic deficits have been identified in individuals with depression and in animal models of epilepsy, as well as in some humans with epilepsy. Vagal nerve stimulation, a treatment already kn own to be effective in the epilepsies, is presently under investigation for effectiveness in affective disorder. New evidence suggests that vagal nerv e stimulation exerts at least some of its therapeutic effects through its c apacity to increase noradrenergic and serotonergic transmission. Finally, e merging evidence supports the concept that some genetic mammalian models of the human epilepsies exhibit analogous manifestations of depression.