Which clinical and experimental data link temporal lobe epilepsy with depression?

Abstract

The association of temporal lobe epilepsy with depression and other neuropsychiatric disorders has been known since the early beginnings of neurology and psychiatry. However, only recently have in vivo and ex vivo techniques such as Positron Emission Tomography, Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in combination with refined animal models and behavioral tests made it possible to identify an emerging pattern of common pathophysiological mechanisms. We now have growing evidence that in both disorders altered interaction of serotonergic and noradrenergic neurons with glutamatergic systems is associated with abnormal neuronal circuits and hyperexcitability. Neuronal hyperexcitability can possibly evoke seizure activity as well as disturbed emotions. Moreover, decreased synaptic levels of neurotransmitters and high glucocorticoid levels influence intracellular signaling pathways such as cAMP, causing disturbances of brain-derived and other neurotrophic factors.These may be associated with hippocampal atrophy seen on Magnetic Resonance Imaging and memory impairment as well as altered fear processing and transient hypertrophy of the amygdala. Positron Emission Tomography studies additionally suggest hypometabolism of glucose in temporal and frontal lobes. Last, but not least, in temporal lobe epilepsy and depression astrocytes play a role that reaches far beyond their involvement in hippocampal sclerosis and ultimately, therapeutic regulation of glial-neuronal interactions may be a target for future research. All these mechanisms are strongly intertwined and probably bidirectional such that the structural and functional alterations from one disease increase the risk for developing the other. This review provides an integrative update of the most relevant experimental and clinical data on temporal lobe epilepsy and its association with depression.

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

“…The effects if IL-1ra led us to propose that the increased IL-1β signaling, which has been a well-established hallmark of temporal lobe epilepsy [15,16], may also be the upstream-most factor that via the hyperactivity of the HPA axis [17][18][19][20] leads to the development of depressive impairments [1]. It has been long suggested that epilepsy and depression share certain pathophysiological mechanisms [21,22]. Given the involvement of IL-1β in epilepsy on the one hand and in depression on the other hand [17,23], it is conceivable to suggest that this cytokine represents one of factors linking mechanisms of the 2 diseases.…”

Epilepsi og depresjon

“…• Endrede konsentrasjoner av hjernens nevrotransmittere, inkludert serotonin, noradrenalin, dopamin, GABA og glutamat • Strukturelle og funksjonelle endringer i frontotemporale områder, spesielt innen de limbiske strukturer Det er i dag flere indikasjoner på at det ved så vel temporallappsepilepsi som depresjoner er en endret interaksjon mellom serotonerge og noradrenerge nevroner på den ene side og glutamaterge systemer på den annen (29). Dette resulterer i abnorme cellulaere nettverk preget av hypereksitabilitet.…”

“…Dette resulterer i abnorme cellulaere nettverk preget av hypereksitabilitet. Man antar at slik nevronal hypereksitabilitet, saerlig i limbiske strukturer, ikke bare kan gi anfall, men også emosjonelle forstyrrelser (29). Redusert serotonerg og noradrenerg aktivitet, som er vist å foreligge hos mange med alvorlige depresjoner, kombinert med høye stressbetingede glukokortikoidnivåer, påvirker danningen av nevrotrope faktorer, noe man tror er forklaringen på hippocampusatrofien man kan se ved begge tilstandene.…”

Seizure Susceptibility and Epileptogenesis in a Rat Model of Epilepsy and Depression Co-Morbidity

“…This was of particular interest because the rate of depression is higher for patients with temporal lobe epilepsy, who suffer from recurrent limbic seizures, than other forms of epilepsy (Kondziella et al, 2007;Piazzini et al, 2001). Although these initial results in the SwLo rats were provocative, they had several major limitations; mortality rate in the 24 h following kainic acid administration was not a specific measure of seizure susceptibility in so far as we did not have direct evidence that the animals died from seizures.…”

“…This distinction is of interest because there is evidence to suggest that temporal lobe epilepsy has an increased association with depression compared with other forms of epilepsy (Kondziella et al, 2007;Piazzini et al, 2001). Our present results appear to partially support this idea, as SwLo rats are also more sensitive to acute limbic seizures induced by pilocarpine, as well as spontaneous limbic seizures in the Figure 1 SwLo rats have a shorter latency to pilocarpine-induced seizures than SwHi rats that is independent of pilocarpine pharmacokinetics.…”