#	Pagina
attuale pagina	/open-h2020/projects/208969/results.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PRE-PSYCH (The Prelude to Psychosis: Brain network analysis in emerging schizophrenia)

Teaser

Summary

Schizophrenia, in its most typical form, is characterized by recurrent episodes of psychosis interspersed with periods of (partial) remission. During a psychotic episode, people may experience hallucinations and delusions and have trouble thinking clearly. The first episode of psychosis tends to occur in adolescence or early adulthood and this is when schizophrenia is usually diagnosed. However, research has shown that changes in behaviour and functioning precede the first psychotic episode. Early signs of impending psychosis include feelings of suspiciousness, social withdrawal, or a drop in school or job performance. These warning signs suggest that the underlying brain disturbance is already ongoing in the so-called prodromal phase, which is period of imminent risk for developing psychosis in adolescents and young adults. The current research project is aimed at clarifying what happens in the brain during this â€˜prelude to psychosisâ€™.

We are especially interested in examining the way that brain regions are interconnected in the prodromal phase preceding the first psychotic episode. This is because long-standing hypotheses on schizophrenia suggest that abnormalities in the communication between brain regions may contribute to the development of psychotic symptoms. In the brain, individually specialized brain regions are connected into a network that is known as the connectome. This network structure allows brain regions to focus on their own specific role while also being able to collaborate with other regions on complex tasks. By examining possible connectome abnormalities in the prodromal phase we hope to learn more about the neurobiology of emerging psychosis.

Clarifying what happens in the brain as psychosis first develops is crucial to the development of novel early detection and intervention strategies for schizophrenia and related spectrum disorders. Mental illness is among the leading cause of disability for adolescents and young adults and gives rise to a broad cost to society through reduced adult productivity and increased healthcare costs. Intervening early in emerging psychotic illness is important on a personal level, because it may mitigate the effects of the illness for youth who are vulnerable to psychosis, and on a societal level by curbing rising mental healthcare costs.

The overarching goal of this project is to assess whether brain network abnormalities underlie the development of psychosis. To this end, we aim to 1) map brain networks of adolescents and young adults showing early signs of impending psychosis, 2) analyse brain network maps for abnormalities in connectivity and network organization, and 3) determine whether, and if so how, brain network abnormalities are predictive of psychosis development.

Work performed

In this project, we use data from the Shanghai At Risk for Psychosis (SHARP) program. As part of this research program, a large sample of adolescents and young adults (mostly between 15 and 25 years of age) with early signs of impending psychosis was recruited at the Shanghai Mental Health Center. Data on clinical symptoms and cognitive functioning, as well as structural and functional brain MRI data are being collected and processed by several labs at Harvard and MIT. For the current project, we used MRI data to reconstruct functional and structural brain networks. We analyzed these brain networks using mathematical tools to study network organization.

We first mapped and analyzed functional brain networks that were reconstructed from so-called functional MRI data. We were specifically interested in the organization of the functional connectome in a number of distinct communities. These communities or modules consist of a set of brain areas that are particularly well connected, but have relatively poor connectivity with regions outside of their community. Our current project shows that at-risk individuals (i.e., youth with early signs of impending psychosis), particularly those that go on to develop a psychotic episode, show abnormalities in the organization of these functional communities. Notably, a number of brain regions that have previously been linked to (early-course) schizophrenia were found to change community affiliation. For example, the superior temporal gyrus, which comprises the auditory cortex and has been implicated in auditory verbal hallucinations, changed affiliation from the primary sensory to the limbic module. These findings are consistent with hypotheses that abnormal interactions between sensory and limbic systems may be involved in the development of psychotic symptoms. These findings were published in Molecular Psychiatry, one of the top-ranking journals in biological psychiatry and neuroscience, and were picked up by several news outlets including SciTech Daily (https://scitechdaily.com/neuroscientists-identify-brain-activity-pattern-linked-to-schizophrenia/)

Next, we performed a prediction analysis to assess if modular connectome organization and functional brain connectivity are predictive of psychosis development. We found that a prediction model that combined connectivity metrics with clinical and cognitive variables yielded the best outcome prediction. This model outperformed connectivity-only and clinical-only prediction models. These findings are currently under review and are expected to be published soon.

In addition to functional connectome reconstructions, we used diffusion-weighted imaging data to map structural brain networks of youth with early signs of impending psychosis. The structural connectome maps will be further analysed during the incoming phase of this research project. We are especially interested in assessing whether possible structural connectome alterations may underlie the observed abnormalities in functional connectome organization.

Final results

We hypothesize that abnormalities in the functional organization of the brain and underlying changes in the architecture of the structural connectome contribute to psychotic symptom development in youth showing early signs of impending psychosis. If confirmed, these findings increase our understanding of the neurobiology of emerging schizophrenia, and may promote the development of early detection and targeted intervention strategies. There are no curative treatment options for schizophrenia, and many researchers in the field think that early detection and intervention is one of the most promising avenues for improving prognosis in schizophrenia and related spectrum disorders. Intervening early in the developing illness may not only prevent full-blown psychosis, but may also support the socio-cognitive development and well-being of youth prone to psychosis thereby helping them reach their full adult potential, and mitigating costs to society as a whole. This project aims to contribute to early intervention by identifying MRI markers of psychotic illness development in young individuals who are vulnerable to psychosis.