Morphometric Brain Abnormalities and Increased Anxiety in a Rat Model of Generalized Epilepsy: Relevance for the Psychiatric Co-morbidies of Epilepsy?

  • Dr Viviane Bouilleret, Departments of Medicine, University of Melbourne, and Department of Neurophysiology and Epilepsy, ApHp, France, France
  • Nigel Jones, Departments of Medicine, RMH, University of Melbourne, The University of Melbourne, Victoria, Australia
  • Bianca Jupp, Departments of Medicine, RMH, University of Melbourne, The University of Melbourne, Victoria, Australia
  • Stefanie Dedeurwaerdere, Departments of Medicine, RMH, University of Melbourne, The University of Melbourne, Victoria, Belgium
  • Denis Velakoulis, Neuropsychiatry Centre, The University of Melbourne, Victoria, Australia
  • Michael Salzberg, Psychiatry, SVH, The University of Melbourne, Victoria, Australia
  • Gary Egan, Florey Neurosciences Institute, The University of Melbourne, Victoria, Australia
  • Terence O'Brien, Departments of Medicine, RMH, University of Melbourne, The University of Melbourne, Victoria, Australia

    • Introduction: Psychiatric co-morbidies frequently occur in patients with epilepsy, but the pathophysiological relationship with the epilepsy remains uncertain. Genetic Absence Epilepsy Rats from Strasbourg (GAERS), bred for their epilepsy phenotype, also exhibit elevated anxiety-like behaviours suggesting a common causality. We examined whether this behavioural disturbance is associated with cerebral morphological alterations. Methods: Volumetric MRI and the Open Field test of anxiety were performed in adult aged matched female GAERS (n=12) and Non-Epileptic Control rats (NEC; n=12). Volumes of selected brain regions was blindly measured on the MRI data, including the ventricles, frontal, medial and posterior cortex, hippocampi, amygdalae, and thalami. Results: GAERS had larger 7.6% mean brain volumes compared to NEC rats (p=0.0074). Relative to whole brain volumes, GAERS showed significantly decreased cortical volume, particularly frontal (right: 6.6%, p=0.038; left 9.4%, p=0.002) but also medial. Conversely, amygdalae (right: 9%, p=0.15; left 14% p=0.012) and ventricular volumes (50%, p=0.01) were increased. GAERS also exhibited greater levels of anxiety-like behaviours compared with NEC rats in the Open Field: reduced distance traveled (p<0.0001), and reduced centre entries (p=0.03). However, within group analyses revealed no direct correlations between individual anxiety and volumes measures. Conclusions: Morphometric brain changes in GAERS could be causally linked to their increased anxiety-like behaviours. Increased amygdala volumes have also been observed in affective disorders in epileptic and non-epileptic patients, and increased ventricular volumes in psychotic disorders. This model may be useful in illuminating the pathogenesis of psychiatric disease generally, as well as modeling the comorbidities of epilepsy.