Abstract

The most common psychiatric disorders that are co-morbid with temporal lobe epilepsy (TLE) are depressive, anxiety, psychotic and personality disorders. This review examines the role of the hippocampus in TLE and associated co-morbidities, and compares the patterns of gene expression in the hippocampus in TLE with patterns in the hippocampus and associated neocortical areas in major depressive disorder and schizophrenia. They may help to provide some insights into the molecular pathophysiology that underlies the psychiatric co-morbidities associated with TLE. Studies to date suggest that hippocampal atrophy is associated with TLE as well as depression and schizophrenia. However, the cause of the atrophy varies: in TLE it is associated with neuronal loss whereas in schizophrenia and major depressive disorder (MDD) there is little or no neuronal loss. Significant gliosis accompanies neuronal loss in TLE, but there is only moderate gliosis in depression and no observable gliosis in schizophrenia. Concordant with astrocytosis there are many astrocyte related genes unregulated in TLE but not in schizophrenia and depression. Down-regulation of mechanisms for the clearance of glutamate is associated with TLE and depression, while activation of immune and inflammatory response genes is seen in TLE and schizophrenia. Down-regulation of genes associated with myelination is common to depression and schizophrenia but not TLE. Synaptic function, ion transport and receptor function genes are down-regulated in TLE and the prefrontal cortex in schizophrenia, whereas neurotransmitter function related genes are up-regulated in the prefrontal cortex in depression.

Keywords: Anxiety disorder, depression, dna microarray analysis, hippocampus, temporal lobe epilepsy, gene expression, schizophrenia