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Neurologic links between epilepsy and depression in women

Is hippocampal neuroplasticity the key?

From the Laboratory of Molecular Neurobiology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary (Dr. Hajszan), the Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut (Dr. Hajszan), and the Department of Biomedical Sciences, Ontario Veterinary College, Guelph, Ontario, Canada (Dr. MacLusky).

Address correspondence to Dr. Tibor Hajszan, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 313, New Haven, CT 06520; email: tibor.hajszan{at}yale.edu

Recent advances in our understanding of the actions of sex steroids on the brain and the pathophysiology of depression have provided a hypothetical framework that may functionally connect epilepsy, ovarian hormone levels, and depression. The hippocampus plays a critical role in both seizure activity and mood disorders, which suggests that pathology in this area of the brain might provide a link between epilepsy and depression. Recent findings support the view that neurogenesis is not the only factor that contributes to the pathomechanism of depression and antidepressant responses, which may involve other hippocampal cellular or molecular changes, or both. Specifically, remodeling of the hippocampal spine synapses may play a significant role in the neurobiology of depression and the effects of antidepressant therapy. Because the effects of estrogens on hippocampal synaptogenesis parallel those of antidepressants, loss of estrogen appears to be a critical contributor to the etiology of depressive disorders. The increased incidence of depression observed in women with epilepsy might therefore reflect a hormonal deficiency state because epilepsy is frequently associated with defects in reproductive function. In women with catamenial epilepsy, changes in gonadal steroid production are seen to link seizure frequency with reproductive state, emphasizing the importance of gonadal steroid levels not only in depression but also in seizure activity. Paradoxical features of epilepsy, i.e., seizure-induced increases in hippocampal neurotrophin expression and neurogenesis, suggest that the most important factor in the neurobiology of depression might be the extent to which the hippocampus can adapt appropriately to changes in the environment through alterations in hippocampal synaptic connectivity.

Publication of this supplement was supported by an educational grant from UCB Pharma Inc. The sponsor has provided the authors with an honorarium for their participation in this project.

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