Using Magnetoencephalography to Investigate Aberrant Neural Synchrony in Prodromal Schizophrenia: A Translational Biomarker Approach

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Schizophrenia is a common mental disorder which is associated with a range of complaints, including voice-hearing (hallucinations) and strange thoughts (delusions) as well as pronounced impairments in memory and attention. Because these symptoms lead to a breakdown of thought-processes, people who are diagnosed with the disorder often cannot live independently and no effective cure currently exists. Schizophrenia is typically diagnosed during the transition from puberty to early adulthood, a period critical for social and occupational development. Accordingly, one important goal of current research is to identify individuals who have an elevated risk of developing schizophrenia prior to the full outbreak of the disorder. If possible, this could reduce or even prevent the profound and long-lasting disruptions that occur to people's lives. One important prerequisite for early intervention are diagnostic techniques which allow reliable prediction of those individuals who may have a particularly high chance of developing the disorder. In the current study, we will use a brain imaging technique, so-called Magnetoencephalograph or MEG, which is a machine that allows the measurement of brain activity with excellent temporal resolution, to develop a novel diagnostic test. In particular, we are interested in finding out whether changes in rhythms of neural activity that the brain generates, so-called "oscillations", may be impaired prior to the outbreak of the disorder and whether those can be useful for predicting the risk of developing schizophrenia. Brain oscillations have been shown to occur during normal brain functioning and are closely linked to the ability to perceive, memorize and attend to information. Moreover, we know from previous studies that patients with established schizophrenia show prominent impairments in the generation of these oscillations which could be one reason for their cognitive difficulties as well as for their hallucinations and delusions. Thus, it appears that brain oscillations could be a key to understanding the causes of the disorder.For the proposed project, we will recruit a large sample of individuals from psychiatric services in Edinburgh and Glasgow who show already behavioural and psychological problems and conduct detailed interviews. If their mental state shows certain signs which could be indicative of schizophrenia but do not meet yet the full diagnostic criteria, we will perform a MEG-measurement as well as a magnetic resonance imaging scan. The latter will also allow us to assess the presence of two neurotransmitters in the brain which are important for proper brain functioning.After the initial brain imaging, we will follow-up these participants for a period of up to two years to assess whether their mental state has changed. If individuals during this period experience a deterioration in their mental health, we will assess them again with an extended interview. In addition to participants at risk for the development of schizophrenia, we will also recruit a group of individuals from the general populations in order to compare their patterns of brain activity with those who may be at-risk for schizophrenia. Through our research, we hope to find a way of diagnosing schizophrenia with brain imaging techniques earlier which could represent an important step to prevent the occurrence of the profound deficits in behavior and brain functioning. Moreover, through our measurements of brain oscillations and associated neurochemicals, we hope to gain in insight into the underlying causes which could be important for the development of novel therapies.