Mechanisms of Psychiatric Comorbidities in Epilepsy

Psychiatric illnesses, including depression and anxiety, are highly comorbid with epilepsy (for review see Josephson and Jetté (Int Rev Psychiatry 29:409-424, 2017), Salpekar and Mula (Epilepsy Behav 98:293-297, 2019)). Psychiatric comorbidities negatively impact the quality of life of patients (Johnson et al., Epilepsia 45:544-550, 2004; Cramer et al., Epilepsy Behav 4:515-521, 2003) and present a significant challenge to treating patients with epilepsy (Hitiris et al., Epilepsy Res 75:192-196, 2007; Petrovski et al., Neurology 75:1015-1021, 2010; Fazel et al., Lancet 382:1646-1654, 2013) (for review see Kanner (Seizure 49:79-82, 2017)). It has long been acknowledged that there is an association between psychiatric illnesses and epilepsy. Hippocrates, in the fourth-fifth century B.C., considered epilepsy and melancholia to be closely related in which he writes that "melancholics ordinarily become epileptics, and epileptics, melancholics" (Lewis, J Ment Sci 80:1-42, 1934). The Babylonians also recognized the frequency of psychosis in patients with epilepsy (Reynolds and Kinnier Wilson, Epilepsia 49:1488-1490, 2008). Despite the fact that the relationship between psychiatric comorbidities and epilepsy has been recognized for thousands of years, psychiatric illnesses in people with epilepsy still commonly go undiagnosed and untreated (Hermann et al., Epilepsia 41(Suppl 2):S31-S41, 2000) and systematic research in this area is still lacking (Devinsky, Epilepsy Behav 4(Suppl 4):S2-S10, 2003). Thus, although it is clear that these are not new issues, there is a need for improvements in the screening and management of patients with psychiatric comorbidities in epilepsy (Lopez et al., Epilepsy Behav 98:302-305, 2019) and progress is needed to understand the underlying neurobiology contributing to these comorbid conditions. To that end, this chapter will raise awareness regarding the scope of the problem as it relates to comorbid psychiatric illnesses and epilepsy and review our current understanding of the potential mechanisms contributing to these comorbidities, focusing on both basic science and clinical research findings.