Do epilepsy and psychiatric disorders share common pathogenic mechanisms? A look at depression and epilepsy

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Abstract

For a long time, epilepsy has been considered a risk factor of depression as its prevalence is higher among patients with epilepsy than the general population. Recent studies, however, have demonstrated that patients with a history of depression are four to six times more likely to develop epilepsy than controls. This bi-directional interaction between depression and epilepsy coupled with the therapeutic effect of various antiepileptic drugs (AEDs) in epilepsy and mood disorders may suggest that common pathogenic mechanisms may be operant in both conditions. Decreased serotonergic (5HT) and noradrenergic (NE) functions have been identified as pivotal pathogenic mechanisms of depression and have been the bases for antidepressant pharmacological treatments. Disturbances of 5HT and NE functions have also been demonstrated in various experimental animal models of epilepsy. For example, two strains of genetic epilepsy prone rats (GEPR), GEPR-3 and GEPR-9 that serve as models of partial epilepsy have innate 5HT and NE pre and post-synaptic transmission deficits, which have been related to the predisposition to experience sound-induced seizures. GEPR-9 s rats have a more pronounced NE transmission deficit and exhibit more severe seizures than GEPR-3 rats. Increments of either NE and/or 5HT transmission can prevent seizure occurrence while reduction will have the opposite effect. Furthermore, the use of selective serotonin-reuptake inhibitors (SSRI), and monoamino oxidase inhibitors (MAOI) have been found to exert anticonvulsant effects in genetically prone epilepsy mice, and baboons and in (non-genetically prone) cats, rabbits and rhesus monkeys. The involvement of common neuronantomical structures in depression and epilepsy further support the hypothesis that both disorders share common pathogenic mechanisms. While involvement of mesial temporal structures and limbic structures of the frontal lobe are rather common among patients with epilepsy and depression, non-epilepsy patients have been found to have atrophy of hippocampal formation, core nuclei of the amygdala, orbitofrontal cortex and cingulate gyrus. The anticonvulsant effect of some AEDs has been shown to be mediated, at least in part by 5HT and NE mechanisms. For example, carbamazepine increases synaptic secretion of 5HT and in GEPR its anticonvulsant protection can be blocked with 5HT depleting drugs. Similarly, destruction of noradrenergic and serotonergic neurons in the rat prevents or reduces significantly the anticonvulsant effect of the vagus nerve stimulator against electroshock or pentylenetetrazol induced seizures. Finally, data from recent studies suggest that the presence of psychiatric disease and in particular depression may be associated with a worse seizure control. In other words, depression could be a marker for 'bad epilepsy'.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalClinical Neuroscience Research
Volume4
Issue number1-2
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Psychiatry
Epilepsy
Depression
Anticonvulsants
Seizures
Prefrontal Cortex
Serotonergic Neurons
Adrenergic Neurons
Electroshock
Pentylenetetrazole
Vagus Nerve
Partial Epilepsy
Papio
Gyrus Cinguli
Carbamazepine
Serotonin Uptake Inhibitors
Frontal Lobe
Therapeutic Uses
Amygdala
Macaca mulatta

Keywords

  • Hippocampal atrophy
  • Major depression
  • Norepinephrine
  • Serotonin

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Neuropsychology and Physiological Psychology

Cite this

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title = "Do epilepsy and psychiatric disorders share common pathogenic mechanisms? A look at depression and epilepsy",
abstract = "For a long time, epilepsy has been considered a risk factor of depression as its prevalence is higher among patients with epilepsy than the general population. Recent studies, however, have demonstrated that patients with a history of depression are four to six times more likely to develop epilepsy than controls. This bi-directional interaction between depression and epilepsy coupled with the therapeutic effect of various antiepileptic drugs (AEDs) in epilepsy and mood disorders may suggest that common pathogenic mechanisms may be operant in both conditions. Decreased serotonergic (5HT) and noradrenergic (NE) functions have been identified as pivotal pathogenic mechanisms of depression and have been the bases for antidepressant pharmacological treatments. Disturbances of 5HT and NE functions have also been demonstrated in various experimental animal models of epilepsy. For example, two strains of genetic epilepsy prone rats (GEPR), GEPR-3 and GEPR-9 that serve as models of partial epilepsy have innate 5HT and NE pre and post-synaptic transmission deficits, which have been related to the predisposition to experience sound-induced seizures. GEPR-9 s rats have a more pronounced NE transmission deficit and exhibit more severe seizures than GEPR-3 rats. Increments of either NE and/or 5HT transmission can prevent seizure occurrence while reduction will have the opposite effect. Furthermore, the use of selective serotonin-reuptake inhibitors (SSRI), and monoamino oxidase inhibitors (MAOI) have been found to exert anticonvulsant effects in genetically prone epilepsy mice, and baboons and in (non-genetically prone) cats, rabbits and rhesus monkeys. The involvement of common neuronantomical structures in depression and epilepsy further support the hypothesis that both disorders share common pathogenic mechanisms. While involvement of mesial temporal structures and limbic structures of the frontal lobe are rather common among patients with epilepsy and depression, non-epilepsy patients have been found to have atrophy of hippocampal formation, core nuclei of the amygdala, orbitofrontal cortex and cingulate gyrus. The anticonvulsant effect of some AEDs has been shown to be mediated, at least in part by 5HT and NE mechanisms. For example, carbamazepine increases synaptic secretion of 5HT and in GEPR its anticonvulsant protection can be blocked with 5HT depleting drugs. Similarly, destruction of noradrenergic and serotonergic neurons in the rat prevents or reduces significantly the anticonvulsant effect of the vagus nerve stimulator against electroshock or pentylenetetrazol induced seizures. Finally, data from recent studies suggest that the presence of psychiatric disease and in particular depression may be associated with a worse seizure control. In other words, depression could be a marker for 'bad epilepsy'.",
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N2 - For a long time, epilepsy has been considered a risk factor of depression as its prevalence is higher among patients with epilepsy than the general population. Recent studies, however, have demonstrated that patients with a history of depression are four to six times more likely to develop epilepsy than controls. This bi-directional interaction between depression and epilepsy coupled with the therapeutic effect of various antiepileptic drugs (AEDs) in epilepsy and mood disorders may suggest that common pathogenic mechanisms may be operant in both conditions. Decreased serotonergic (5HT) and noradrenergic (NE) functions have been identified as pivotal pathogenic mechanisms of depression and have been the bases for antidepressant pharmacological treatments. Disturbances of 5HT and NE functions have also been demonstrated in various experimental animal models of epilepsy. For example, two strains of genetic epilepsy prone rats (GEPR), GEPR-3 and GEPR-9 that serve as models of partial epilepsy have innate 5HT and NE pre and post-synaptic transmission deficits, which have been related to the predisposition to experience sound-induced seizures. GEPR-9 s rats have a more pronounced NE transmission deficit and exhibit more severe seizures than GEPR-3 rats. Increments of either NE and/or 5HT transmission can prevent seizure occurrence while reduction will have the opposite effect. Furthermore, the use of selective serotonin-reuptake inhibitors (SSRI), and monoamino oxidase inhibitors (MAOI) have been found to exert anticonvulsant effects in genetically prone epilepsy mice, and baboons and in (non-genetically prone) cats, rabbits and rhesus monkeys. The involvement of common neuronantomical structures in depression and epilepsy further support the hypothesis that both disorders share common pathogenic mechanisms. While involvement of mesial temporal structures and limbic structures of the frontal lobe are rather common among patients with epilepsy and depression, non-epilepsy patients have been found to have atrophy of hippocampal formation, core nuclei of the amygdala, orbitofrontal cortex and cingulate gyrus. The anticonvulsant effect of some AEDs has been shown to be mediated, at least in part by 5HT and NE mechanisms. For example, carbamazepine increases synaptic secretion of 5HT and in GEPR its anticonvulsant protection can be blocked with 5HT depleting drugs. Similarly, destruction of noradrenergic and serotonergic neurons in the rat prevents or reduces significantly the anticonvulsant effect of the vagus nerve stimulator against electroshock or pentylenetetrazol induced seizures. Finally, data from recent studies suggest that the presence of psychiatric disease and in particular depression may be associated with a worse seizure control. In other words, depression could be a marker for 'bad epilepsy'.

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