Abstracts

Rationale: -Aminobutyric acid (GABA) system is known to be involved in seizure activity as well as in anxiety and depression. However, there is no information concerning changes of this system in the neocortex of patients with temporal lobe epilepsy (TLE) and comorbid psychiatric disorders. The aim of this study was to investigate alterations of GABA system in temporal neocortex of patients with pharmacoresistant TLE and comorbid anxiety and depression.Methods: Experiments were designed to evaluate binding to GABAA, GABAB and benzodiazepine (BDZ) receptors; G protein activation induced by selective agonists to GABAB receptors, and tissue content of GABA in temporal neocortex of patients with pharmacoresistant TLE and comorbid anxiety and depression (n=9). The results obtained were compared with data of patients with pharmacoresistant TLE without comorbid neuropsychiatric disorders (n=19) and tissue obtained from autopsy samples (n=6). In addition, we sought to identify the possible influence of clinical factors (age of patient, age of seizure onset, duration of epilepsy and frequency of ictal events) on alterations of GABA system. Results: Neocortex of patients with TLE with comorbid anxiety and depression demonstrated lower tissue content of GABA (42%, p<0.05), a situation that correlated with the higher seizure frequency (r= 0.5822, p<0.05). The neocortex of these patients also showed increased GABAB binding (layers III-IV, 102%, p<0.01; layers V-VI, 88%, p<0.01). However, reduced GABAB-induced G protein activation was detected in all neocortex (layers I-II, 47%, p<0.05; layers III-IV, 56%, p<0.01; and layers V-VI, 46%, p<0.01), a situation that correlated with the seizure frequency in layers III-IV (r=0.7380, p<0.05) and layers V-VI (r=0.8859, p<0.01). In patients with TLE without neuropsychiatric alterations, autoradiography experiments revealed augmented BDZ binding in all neocortical layers (layers I-II, 86%, p<0.05; layers III-IV, 58%, p<0.05; and layers V-VI, 103%, p<0.001), a situation that correlated with the lower seizure frequency (layers III-IV, r= 0.5285, p<0.05; and layers V-VI, r= 0.4914, p<0.05) and lower duration of epilepsy (layers III-IV, r=0.5285, p<0.05; layers V-VI, r=0.4914, p<0.05). The neocortex of these patients also demonstrated high GABAB binding (layers III-IV, 74%, p<0.01; layers V-VI, 90%, p<0.01), but lower GABAB-induced G protein activation restricted to deep cortical layers (layers V-VI, 39%, p<0.05). No further changes were detected.Conclusions: Our present data provide strong evidence that temporal neocortex of patients with TLE and comorbid anxiety and depression shows important changes in GABA tissue content and GABAB induced neurotransmission.