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The Neuroscientist, Vol. 13, No. 4, 392-404 (2007)
DOI: 10.1177/10738584070130041101

Bipolar Disorder and Epilepsy: A Bidirectional Relation? Neurobiological Underpinnings, Current Hypotheses, and Future Research Directions

Marianna Mazza, MD, PhD

Institute of Psychiatry, Bipolar Disorders Unit, Catholic University of Sacred Heart, Rome, Italy, marianna.mazza{at}rm.unicatt.it

Marco Di Nicola

Institute of Psychiatry, Bipolar Disorders Unit, Catholic University of Sacred Heart, Rome, Italy

Giacomo Della Marca

Department of Neurosciences, Epilepsy Center, Catholic University of Sacred Heart, Rome, Italy

Luigi Janiri

Institute of Psychiatry, Bipolar Disorders Unit, Catholic University of Sacred Heart, Rome, Italy

Pietro Bria

Institute of Psychiatry, Bipolar Disorders Unit, Catholic University of Sacred Heart, Rome, Italy

Salvatore Mazza

Department of Neurosciences, Epilepsy Center, Catholic University of Sacred Heart, Rome, Italy

A number of studies have demonstrated that affective disorders in epilepsy represent a common psychiatric comorbidity; however, most of the classic neuropsychiatric literature focuses on depression, which is actually prominent, but little is known about bipolar depression, and very little about mania, in epilepsy. Biochemical, structural, and functional abnormalities in primary bipolar disorder could also occur secondary to seizure disorders. The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. 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. Common mechanisms at the level of ion channels might include the antikindling 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 disorder and epilepsy. Mania, which is the other side of the coin in affective disorders, may represent a privileged window into the neurobiology of mood regulation and the neurobiology of epilepsy itself. Future research on intracellular mechanisms might become decisive for a better understanding of the similarities between these two disorders. NEUROSCIENTIST 13(4):392—404, 2007. DOI: 10.1177/1073858407301117

Key Words: Epilepsy • Bipolar disorder • Mania • Kindling • Second messengers • Neurotransmitters • Ion channels


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