title: Contribution of amygdala pathology to comorbid emotional disturbances in temporal lobe epilepsy.
abstract: The amygdala contributes to the generation and propagation of epileptiform activity in temporal lobe epilepsy (TLE). Ictal symptoms such as fear, dreamy states (déjà vu, memory flashbacks, experiential hallucinations), epigastric auras, or sympathetic outflow with cardiovascular changes are often linked to a seizure focus in the amygdala. However, the amygdala may also play a role in comorbid anxiety, depression, and other psychiatric symptoms experienced in the interictal phase, especially in pharmacoresistant TLE. The few studies available on TLE-related alterations in surgical amygdala specimens indicate loss of both excitatory spiny projection neurons as well as interneurons in nuclei with a cortex-like architecture, which may influence mechanisms of feedforward and feedback inhibition. Studies of the human amygdala indicate global alterations in the density of AMPA/kainate, metabotropic glutamate, γ-aminobutyric acid type A (GABAA ), muscarinic M2 and M3, serotonergic 5-HT1A, and adrenergic α1 receptors. Also, amygdala GABAergic and neuropeptide Y (NPY) systems affected in human TLE are both involved in antiepileptic and anxiolytic effects. Experimental and human positron emission tomography studies indicate changes in amygdala serotonergic, NPY Y1 receptor, neurokinin, and opioid systems in emotional disturbances in TLE. Of particular interest is the reduction in amygdala volume in conjunction with ictal fear, seizure focus in the amygdala, and amygdala and hippocampal sclerosis in TLE patients. In contrast, patients with interictal depression often have an intact or even enlarged amygdala and a negative MRI associated with amygdala hypometabolism, which can be associated with limbic autoimmune encephalitis. These findings suggest a differential role of TLE-related amygdala changes in ictal and interictal emotional disturbances.
authors.affiliation: Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, Nebraska.|Department of Anatomy and Neuroscience, University College, Cork, Ireland.
authors.forename: Deniz
authors.initials: D
authors.lastname: Yilmazer-Hanke
authors.affiliation: Department of Anatomy and Neuroscience, University College, Cork, Ireland.|Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elaine
authors.initials: E
authors.lastname: O'Loughlin
authors.affiliation: Department of Anatomy and Neuroscience, University College, Cork, Ireland.|Graduate Entry Medical School, University of Limerick, Limerick, Ireland.
authors.forename: Kieran
authors.initials: K
authors.lastname: McDermott
mesh_terms: D000342:Affective Symptoms / Q000209:etiology* / Q000473:pathology*; D000679:Amygdala / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000150:complications*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter
keywords: amygdaloid sclerosis; anxiety and depression; ictal fear; interictal psychopathology; neurotransmission; seizure