Biomarkers of Epileptogenesis: Psychiatric Comorbidities (?)

Abstract

The last decade has witnessed a significant shift on our understanding of the relationship between psychiatric disorders and epilepsy. While traditionally psychiatric disorders were considered as a complication of the underlying seizure disorder, new epidemiologic data, supported by clinical and experimental research, have suggested the existence of a bidirectional relation between the two types of conditions: not only are patients with epilepsy at greater risk of experiencing a psychiatric disorder, but patients with primary psychiatric disorders are at greater risk of developing epilepsy. Do these data suggest that some of the pathogenic mechanisms operant in psychiatric comorbidities play a role in epileptogenesis? The aim of this article is to review the epidemiologic data that demonstrate that primary psychiatric disorders are more frequent in people who develop epilepsy, before the onset of the seizure disorder than among controls. The next question looks at the available data of pathogenic mechanisms of primary mood disorders and their potential for facilitating the development and/or exacerbation in the severity of epileptic seizures. Finally, we review data derived from experimental studies in animal models of depression and epilepsy that support a potential role of pathogenic mechanisms of mood disorders in the development of epileptic seizures and epileptogenesis. The data presented in this article do not yet establish conclusive evidence of a pathogenic role of psychiatric comorbidities in epileptogenesis, but raise important research questions that need to be investigated in experimental, clinical, and population-based epidemiologic research studies.

Epileptogenesis

“…1B). Epileptogenesis is often associated with comorbidities, which may originate from overlapping networks (Kanner et al 2014) and/or result from the effects of SRSs. Thus, disease or syndrome modification has two components: antiepileptogenesis (AEG) and comorbidity modification.…”

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

“…Epidemiological data demonstrate that primary psychiatric disorders are more frequent in people who develop epilepsy before the onset of the seizure disorder than among controls (Kanner et al, 2014). This may support the notion that there may be neurological underpinnings of metabolic syndrome, drug addiction, bipolar disorder and epilepsy (Amann and Grunze, 2005;Kenny, 2011).…”

“…Bipolar disorder like Alzheimer's disease and type 2 diabetes mellitus may be an age-related disorder where brain structural changes, cognitive deficits, oxidative stress imbalance, Aβ deposits, immunosenescence, telomere shortening and neurotrophin deficiency are important pathophysiogic canges (Rizzo et al, 2014) and metformin is reported to prevent premature senescence associated with agerelated illnesses (Oriaifo et al, 2015) and able to correct the pathophysiologic changes. Animal models support a potential role of pathogenic mechanisms of mood disorders in the development of epileptic seizures and epileptogenesis (Kanner et al, 2014). Depression and manic episodes are described in bipolar disorder and in epilepsy (Kudo et al, 2001;Epps et al, 2012) underlining a bidirectional relationship.…”

Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

“…Previous studies have documented the linkage between epilepsy and depression both in 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 20 preclinical models and in humans [70,71]. Regarding WAG/Rij rats, it has also been hypothesized that some common, currently unknown, mechanisms could be responsible for the appearance of absence seizures and low-grade depression (dysthymia) in this strain, with seizure activity being required for the expression of depressive-like behavior [26,72] even though some exceptions exist [27,40,41].…”