Depression and Anxiety in the Epilepsies: from Bench to Bedside

Depression and anxiety substantially contribute to interictal disability in patients with epilepsy (PWE). This review summarizes current studies that shed light on mechanisms of comorbidity.

Mounting epidemiological data implicate shared risk factors for anxiety/depression and seizure propensity, but these remain largely elusive and probably vary by epilepsy type. Within PWE, these symptoms appear to be associated with unique genetic, neuropathological, and connectivity profiles. Temporal lobe epilepsy has received enormous emphasis particularly in preclinical studies of comorbidity, where candidate neurobiological mechanisms underlying bidirectionality have been tested without psychopharmacological confounds. Depression and anxiety in epilepsy reflect dysfunction within broadly distributed limbic networks that may be the cause or consequence of epileptogenesis. In refractory epilepsy, seizures and/or certain anticonvulsants may distort central emotional homeostatic mechanisms that perpetually raise seizure risk. Developing future safe and effective combined anticonvulsant-antidepressant treatments will require a detailed understanding of anatomical and molecular nodes that pleiotropically enhance seizure risk and negatively alter emotionality.