Network Dysfunction in Comorbid Psychiatric Illnesses and Epilepsy

Abstract

<jats:p> The episodic nature of both epilepsy and psychiatric illnesses suggests that the brain switches between healthy and pathological states. The most obvious example of transitions between network states related to epilepsy is the manifestation of ictal events. In addition to seizures, there are more subtle changes in network communication within and between brain regions, which we propose may contribute to psychiatric illnesses associated with the epilepsies. This review will highlight evidence supporting aberrant network activity associated with epilepsy and the contribution to cognitive impairments and comorbid psychiatric illnesses. Further, we discuss potential mechanisms mediating the network dysfunction associated with comorbidities in epilepsy, including interneuron loss and hypothalamic–pituitary–adrenal axis dysfunction. Conceptually, it is necessary to think beyond ictal activity to appreciate the breadth of network dysfunction contributing to the spectrum of symptoms associated with epilepsy, including psychiatric comorbidities. </jats:p>

Behavioral phenotypes of temporal lobe epilepsy

“…Furthermore, the underlying etiology and prospective course of identified behavioral phenotypes remain critical issues for future research including the application of more sophisticated imaging of potential underlying neurobiological abnormalities with a focus on disruptions of networks integral for emotional‐behavioral status 56 . Also important will be the pursuit of phenotypic membership with an actuarial approach, one that focusses on classification of individual patients with isolated impairments as has been undertaken in cognitive research 11,13 .…”

“…Furthermore, the underlying etiology and prospective course of identified behavioral phenotypes remain critical issues for future research including the application of more sophisticated imaging of potential underlying neurobiological abnormalities with a focus on disruptions of networks integral for emotional-behavioral status. 56 Also important will be the pursuit of phenotypic membership with an actuarial approach, one that focusses on classification of individual patients with isolated impairments as has been undertaken in cognitive research. 11,13 Finally, the degree to which these behavioral phenotypes generalize to other epilepsy syndromes versus require syndrome-specific modifications will help to inform the relationship of the evolving taxonomy of the neurobehavioral comorbidities of epilepsy to the classification of the epilepsies.…”

Depressive and Anxiety Symptoms Are Predictors of Seizure Recurrence in Adults With Newly Diagnosed Epilepsy

“…Evidence also showed the alterations of the white matter network and structural connectivity in non-lesional temporal lobe epilepsy ( 25 ). Psychiatric disorders involve network-level changes and network dysfunction, and network dysfunction is commonly manifested as seizures in epilepsy ( 26 ). Additionally, a hyperactivity of the hypothalamic—pituitary—adrenal (HPA) axis was associated with cortical changes especially in the volume of hippocampus and frontal lobes, which not only lead to depression but also contribute to epilepsy ( 27 , 28 ).…”

Increased resting state connectivity in the anterior default mode network of idiopathic epileptic dogs

“…Comorbidities are increasingly recognized in canine epilepsy 29 , 30 , 33 , 34 . Changes in RSN concurrent with anxiety and other behavioral comorbidities have been investigated in humans 19 . In people affected by anxiety decreased and increased activation of the anterior DMN 69 in the region of the anterior cingulate cortex 70 – 72 have been found, consistent with impaired function of the DMN during regulation of emotions 73 .…”

“…Epilepsy is commonly accompanied by neurobehavioral and/or psychiatric comorbidities such as depression, anxiety and cognitive impairments 17 , 18 . Emerging evidence suggests that network alterations detected by rs-fMRI do not only correlate with generation of ictal activity, but may also contribute to neurobehavioral comorbidities 19 .…”