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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Dean F. Salisbury, University of Pittsburgh, USA
- Second opponent: Associate Professor Mei-Hua Hall, Harvard Medical School, USA
- Third member and chair of the evaluation committee: Professor Soili Marianne Lehto, University of Oslo
Chair of the Defence
Professor Emeritus Leif Ingvald Gjerstad, University of Oslo
Principal Supervisor
Professor Torbjørn Elvsåshagen, University of Oslo
Summary
Psychotic disorders are characterized by disturbed experience of reality and often result in long-term functional disability. Limited knowledge about the disease mechanisms constitutes an obstacle to the development of more effective therapies.
The aim of the thesis was to investigate fundamental aspects of psychosis pathophysiology using the electroencephalographic (EEG) marker Mismatch Negativity (MMN), which appear to be mediated by glutamatergic neurotransmission and has been purported to index the capacity of the brain to update sensory models of the environment. A cohort of participants with schizophrenia (SCZ), bipolar disorder (BD) and healthy controls (HC) underwent EEG, magnetic resonance imaging and genotyping as well as detailed clinical characterization. In a subgroup of participants (n = 14), small 3-dimentional cortical spheroids consisting of neural tissue, was cultured from induced pluripotent stem cells obtained from skin biopsies.
We replicated previous findings that MMN is impaired in SCZ. MMN impairment was driven by the male participants suggesting a protective effect of female sex. Furthermore, among the male participants MMN was equally impaired in SCZ and in BD with a history of psychosis, suggesting that MMN impairment may index a transdiagnostic feature across the psychosis spectrum.
MMN did not correlate with genetic risk for psychotic disorders but were positively associated with volumes of several higher order thalamic nuclei responsible for conveying transcortical information flow.
Positive associations were found between donor MMN and two specific neuronal markers of cortical spheroids, the interneuron marker somatostatin (SST) and a protein – GRIN2A- associated with glutamatergic neurotransmission.
The study adds new knowledge of the neural basis of psychotic disorders employing novel technologies that may pave way for future treatments benefitting patients suffering from severe mental disorders.
Additional information
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