Neuropsychiatric Symptoms of Epilepsy

16 Epilepsy in Psychiatric Disorders
293
mechanisms at the level of ion channels might include the anti-kindling and the
calcium- antagonistic and potassium outward current-modulating properties of antiepileptic
drugs. All these lines of research appear to be converging on a richer
understanding of neurobiological underpinnings between bipolar disorders and epilepsy.
In bipolar patients, changes in second-messenger systems, such as G-proteins,
phosphatidylinositol, protein kinase C, myristoylated alanine-rich C kinase substrate,
or calcium activity, have been described along with changes in c-fos expression
[ 23 ]. Future research on intracellular mechanisms might become decisive for a
better understanding of the similarities between these two disorders [ 24 ].
Psychosis and Epilepsy
The view of psychosis, and more specifically schizophrenia, as a neuropsychiatric
condition contributed to a scientific notion that structural brain abnormalities in
these patients could directly contribute to an increased risk of seizures [ 25 ]. Patients
with schizophrenia have been reported to have an 11-fold increase in the prevalence
of comorbid epilepsy [ 26 ]. The most recent evidence suggests that there is significant
overlap in epidemiological, clinical, neuropathological, and neuroimaging features
of the two diseases, which share biological liability. Those include ventricular
enlargement in both conditions, the leucine-rich glioma inactivated (LGI) family
gene loci overlap in both conditions, and other similarities [ 25 ]. Pathological studies
of the brains of schizophrenic patients have revealed disorganization of the typical
laminar structure of the hippocampus [ 27 ]. Pathological abnormalities in the hippocampus
might result in the widespread disruption of the corticolimbic structures,
such as the prefrontal cortex, with consequent development of schizophrenic symptoms
[ 27 ]. In 1953, Landolt introduced EEG recordings as a means of better elucidating
this peculiar antagonism, and coined the term “paradoxical” or “forced EEG
normalization” (FN) [ 28 ], stating that “FN is a phenomenon characterized by the
fact that, with the occurrence of psychotic states, the EEG becomes less abnormal,
or entirely normal, as compared with previous and subsequent EEG findings.”
Various mechanisms have been proposed as underlying the antagonistic relationship
between epileptic activity and psychosis, including an imbalance of inhibition and
over-activation, kindling processes, the propagation of epileptic discharges along
unusual pathways, and neurotransmitter alterations [ 29 ].
Seizures and Psychotropic Drugs
A wide range of substances, including psychotropic drugs, increase the risk of epileptic
seizures. In a systematic review, Ruffmann et al. [ 30 ] addressed the issue of
the epileptogenic potential of marketed drugs given at therapeutic doses. The
authors clinically appraised the available reports emphasizing that a correlation