Genetic and autoimmune modulators of brain function in neuropsychiatric illness and health

In the present thesis, the synergetic interaction between the nervous and immune systems and the potential pathological outcomes mediated by autoimmune processes targeting the brain was addressed, with a particular focus on autoantibodies targeting NMDAR. The first two projects were designed to understand the role of these autoantibodies beyond this pathological condition and gain insight to its effects upon access to the brain. Specifically, Project I aimed at (i) determining the functional properties of NMDAR-ABs of different isotypes; for this purpose a new assay employing human induced pluripotent stem cell-derived neurons was developed. (ii) Identifying which NMDAR epitopes are recognized by these autoantibodies. Project II focused on (i) determining if these NMDAR-AB are present and functional in other mammal species; (ii) assessing the protective role of the BBB and the effects of endogenously produced NMDAR-AB on the brain, in the presence of an open BBB. Additionally, I have briefly mentioned that disruption of the balance between excitation and inhibition in the brain can contribute to brain diseases as autism and schizophrenia. The contributors for such disruption are not completely understood and might have a common ground between diseases. In Project III, we focused on dissecting the relationship between the severity of autistic traits in schizophrenic patients and imbalances in excitation and inhibition. Specifically, using transcranial magnetic stimulation (TMS), we aimed at determining if individuals with low severity of autistic traits and individuals with high severity of autistic traits would differ in terms of glutamatergic or GABAergic neurotransmission