Review Anxiety symptoms in epilepsy: Salient issues for future research ☆ Hamada Hamid a , Alan B. Ettinger b, ⁎, Marco Mula c a Yale University and VA Connecticut Healthcare System, New Haven, CT, USA b Epilepsy Wellness Center, Neurosciences Institute at the Winthrop University Hospital, Mineola, NY, USA c Department of Clinical and Experimental Medicine, Amedeo Avogadro University, Division of Neurology, University Hospital Maggiore della Carità, Novara, Italy abstract article info Article history: Received 22 April 2011 Accepted 24 April 2011 Available online 8 July 2011 Keywords: Anxiety Mood disorders Neuroimaging This paper reviews the distinct symptom profile, epidemiology, pathogenesis, assessment, and treatment of anxiety disorders. It highlights emerging neuroimaging research in mood and anxiety disorders in people with epilepsy. While structural neuroimaging has implicated frontal temporal grey matter structures in mood and anxiety disorders, diffusion tensor imaging and magnetic resonance spectroscopy (MRS) show promise in elucidating white matter changes. In addition, future MRS studies may demonstrate changes in glutamate and gamma-aminobutyric acid (GABA) levels in these regions and hopefully help inform response to treatment. © 2011 Elsevier Inc. All rights reserved. 1. Introduction Although the importance of the psychiatric comorbidities of epilepsy has been increasingly recognized in recent years, most attention has been focused on depression, with relatively less focus on anxiety symptoms. Yet, anxiety is commonly comorbid with depression and is believed to have a prevalence rate comparable to that of depression. While many bemoan the inadequate screening for depression in patients with epilepsy evaluated in typical office practices, screening for anxiety symptoms is virtually never performed. Potentially highly effective treatments for anxiety in patients with epilepsy are therefore often neglected. Furthermore, overlap in symptomatology between depres- sion and anxiety potentially obscures the distinctive features of anxiety that warrant its own evaluation and appropriate treatment. Anxiety may play a key role in effecting suicidality among depressed patients with epilepsy [1]. We therefore contend that the study of anxiety symptoms of epilepsy deserves heightened attention and propose that the areas outlined in this article should be the focus of future intensive research. 2. Clarification of the potentially unique nature of anxiety symptoms in epilepsy and the differentiation of anxiety from depression Although the “bible” of psychiatry, that is, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), classifies a number of disorders under the general category Anxiety Disorders, it remains unclear how applicable this classification system is as applied to patients with epilepsy. Current categories include generalized anxiety disorder, panic disorder (with or without agoraphobia), obsessive– compulsive disorder, posttraumatic stress disorder (PTSD) and phobias, and anxiety arising as a direct physiological consequence of a medical disease process. Studies are needed to examine the symptoms specific to anxiety in epilepsy and how they differ from the anxiety symptoms in primary anxiety disorders and from anxiety symptoms encountered in other medical and central nervous system disorders. There are very few studies, for example, on the rates, etiologies, and nature of obsessive– compulsive disorder in epilepsy and how it is best treated in the epilepsy setting. Few studies have considered seizures as a potential “trauma” inducing a PTSD syndrome; yet this may in fact play an important role in generating anxiety symptoms. Furthermore, studies are needed to clarify how anxiety symptoms differ from those of depression, which, in patients with epilepsy, is likely to accompany anxiety, and in what circumstances does anxiety occur in isolation. 3. Pathogenesis of anxiety in epilepsy 3.1. Psychodynamic, learning, and cognitive-behavioral underpinnings Theories on the pathogenesis of primary anxiety disorders abound; some of these theories may apply to anxiety in epilepsy, but little formal study has been performed in this area. Psychodynamic perspectives that originate in Freudian theory posit that anxiety symptoms relate to obstruction of libidinal drives and intrapsychic conflicts [2]. More modern approaches emphasize anxiety as a reaction to real or imagined threats. Little is known about how seizures and their complications may be perceived by the patient as a threat to Epilepsy & Behavior 22 (2011) 63–68 ☆ From a special issue of Epilepsy & Behavior: "The Future of Clinical Epilepsy Research" in which articles synthesize reviews from senior investigators with the contributions and research directions of promising young investigators. ⁎ Corresponding author at: Neurological Surgery P.C., 1991 Marcus Avenue, Suite 108, Lake Success, NY 11042, USA. E-mail address: aettinge@yahoo.com (A.B. Ettinger). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.04.064 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh