الفهرس 
SERETONIN METABOLISMOnly 14 pages are availabe for public view
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Abstract
Epilepsy is a common group of neurological disorders
defined by unprovoked seizures; Seizures can be
distressing, harmful and even fatal. There is a high incidence of
psychiatric comorbidity in people with epilepsy particularly
depression, especially in (TLE). As temporal lobe epilepsy with
Mesial temporal sclerosis is focal type of epilepsy resistant to
medical treatment affected by stressors. Stressors at all
developmental stages – prenatal, postnatal and in adult life
which have effect in brain serotonergic function.
Serotonergic receptors play a role epileptogenesis in the
CNS, e.g. 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3 and 5-
HT7 receptors are present on cortical and/or hippocampal
glutamatergic or GABAergic neurons or terminals. Serotonin is
monoamine neurotransmitter found centrally & peripherally
with several different types (5-HT) receptors 7 distinct families
& more than 20 subtypes.
There is decrease in 5HT1A receptors in TLE and
decreased hippocampal volume that is attributed to psychiatric
and cognitive impairment.
Epilepsy is usually associated with depression which is
suggestive of a common etiology. Disrupted production of
adult-born hippocampal granule cells in both disorders may
contribute to this coincidence. chronic stress and depression
are associated with decreased granule cell neurogenesis. Epilepsy is associated with increased production – but
aberrant integration – of new cells early in the disease and
decreased production late in the disease too. In both cases, this
review suggests these changes in neurogenesis play important
roles in their respective diseases. Morever, they both result
from dysregulation of hypothalamo pituitary adreno cortical
axis and corticosteroids.
If there is shared underlying pathology that can lead to both
seizures and depression, then it would be expected that treatments
for one condition would improve the symptoms of the other. This
appears to be the case, since some treatments for depression are
effective against seizures, and some anticonvulsants are effective
in management of mood/affective disorders.
Exposure to older generations of antidepressants (notably
tricyclic antidepressants and bupropion) can increase seizure
frequency. However, growing evidence suggests that newer
(‗second generation‘) antidepressants, such as selective
serotonin reuptake inhibitors or serotonin-noradrenaline
reuptake inhibitors, have markedly less effect on excitability
and may lead to improvements in epilepsy severity.
In general, an increase in extracellular 5-HT levels
inhibits many types of seizures and a decrease does the
opposite.Several anti-epileptic drugs including phenytoin,
carbamazepine, valproic acid, lamotrigine and zonisamide all
cause an increase in extracellular 5-HT, and the elevated 5-HT
is thought to contribute to their mechanism of action.Sudden unexpected death in epilepsy (SUDEP) is one of
epileptic comorbidities has a link to serotonergic pathway, as
the frequency of respiratory arrest is markedly reduced by
pretreatment with SSRIs.
Finally, selective Seretonin Reuptake inhibitors should
be further studied in higher doses for management of refractory
epilepsy, regarding the potential benefit, to assess its
anticonvulsive effect, as epilepsy is associated with several
serotonin-related comorbidities.