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Brain structural and neurofunctional correlates of liability to psychosis

English title Brain structural and neurofunctional correlates of liability to psychosis
Applicant Borgwardt Stefan
Number 119382
Funding scheme Ambizione
Research institution Psychiatrische Universitätspoliklinik Allg. Psychiatrie ambulant c/o Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Neurology, Psychiatry
Start/End 01.04.2008 - 31.03.2011
Approved amount 608'651.00
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All Disciplines (2)

Discipline
Neurology, Psychiatry
Mental Disorders, Psychosomatic Diseases

Keywords (10)

neuroimaging; psychosis; schizophrenia; MRI; at-risk mental state; prodrome; fMRI; genetics; cognition; brain structure

Lay Summary (English)

Lead
Lay summary
Early clinical intervention in schizophrenia has recently become a major objective of mental health services, while research on the early phase of the disorder may provide important clues to the mechanisms underlying schizophrenia. Thus, the identification of a syndrome or set of traits that reflect a predisposition to schizophrenia is fundamental from both a clinical and a research perspective. A clinical high-risk strategy (i.e. at-risk mental state, ARMS; ultra high risk, UHR) focuses on individuals who are considered to be at an increased risk for psychotic disorders based primarily on the presence of ‘attenuated’ psychotic symptoms, brief limited intermittent psychotic symptoms and on a recent decline in functioning, characteristics that have been shown to significantly increase the risk for imminent onset of psychosis. Schizophrenia is associated with robust neuroanatomical abnormalities including ventricular enlargement and reduced frontal and temporal lobe volume. However the extent to which these are related to the vulnerability to the disorder, rather than the illness itself, is less certain. Only very little is known about the nature of structural and neurofunctional brain abnormalities in this group with a liability to psychosis.The objective of the present project is to develop a better understanding of the neurobiological mechanisms of liability for psychosis. This will be achieved by using Magnetic Resonance Imaging (MRI) to examine brain structural and functional correlates of the at-risk mental state (ARMS). Furthermore, cognitive and genetic data will be obtained and associated with neuroimaging data. MRI will be used to examine distinct neurobiological traits, in particular by assessing regional gray and white matter volumes, covariance between gray matter volume in different regions, cortical thickness distribution, region-of-interest analyses and neural function during memory and response inhibition tasks and effective connectivity between regions.Brain structural and functional correlates of the at-risk mental state and first-episode subjects will advance our understanding of the mechanisms underlying the development of psychosis. Also, a better understanding of genetic influences on brain structure and function and structure-cognition associations of the brain will shed light on the neurobiological mechanisms that mediate contribution to key aspects of cognitive abnormalities in schizophrenia and its prodromal state. Determining the trajectory of structural and neural abnormalities will improve our knowledge of the neuronal circuits and cognitive processes that are implicated in biological vulnerability to mental illness. This may facilitate the identification of individuals at increased risk and improve clinical intervention to be targeted.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
159554 What Protects Patients at Risk for Psychosis? A Long-Term Follow-up Study 01.07.2015 Project funding

Abstract

BackgroundEarly clinical intervention in schizophrenia has recently become a major objective of mental health services, while research on the early phase of the disorder may provide important clues to the mechanisms underlying schizophrenia. Thus, the identification of a syndrome or set of traits that reflect a predisposition to schizophrenia is fundamental from both a clinical and a research perspective. A clinical high-risk strategy (i.e. at-risk mental state, ARMS; ultra high risk, UHR) focuses on individuals who are considered to be at an increased risk for psychotic disorders based primarily on the presence of ‘attenuated’ psychotic symptoms, brief limited intermittent psychotic symptoms and on a recent decline in functioning, characteristics that have been shown to significantly increase the risk for imminent onset of psychosis. Schizophrenia is associated with robust neuroanatomical abnormalities including ventricular enlargement and reduced frontal and temporal lobe volume. However the extent to which these are related to the vulnerability to the disorder, rather than the illness itself, is less certain. Only very little is known about the nature of structural and neurofunctional brain abnormalities in this group with a liability to psychosis.Aim of the StudyThe objective of the present project is to develop a better understanding of the neurobiological mechanisms of liability for psychosis. This will be achieved by using multimodal Magnetic Resonance Imaging (MRI) to examine brain structural and functional correlates of the at-risk mental state (ARMS).Working HypothesisThe overall hypothesis is that subjects with a liability for psychosis and an at-risk mental state (ARMS) will show brain structural and neurofunctional abnormalities relative to controls that are qualitatively similar to those in patients with first episode schizophrenia.Experimental Design and MethodsSubjects with an at-risk mental state (ARMS) and patients experiencing their first episode of psychosis as well as healthy controls are recruited through the specialised clinic for the early detection of psychosis at the Psychiatric Outpatient Department, University Hospital in Basel, Switzerland (FEPSY study). Subjects are scanned using a SIEMENS MAGNETOM Allegra 3.0 T scanner at the University Hospital Basel. Structural three-dimensional volumetric spoiled gradient recalled echo sequences and functional MR images demonstrating BOLD contrast will be acquired from all subjects at baseline and follow up. To increase the power of the study and to maximize the sample size we have established a collaboration with another early detection centres such as the early detection of psychosis study (OASIS) at the Institute of Psychiatry (Professor Philip McGuire). Structural and functional magnetic resonance imaging data from the FEPSY (Basel) and the OASIS (London) study will be utilised. The clinical diagnostic criteria as well as scanner modalities in Basel and London are the same, and the services (FEPSY and OASIS) analogous. Furthermore, cognitive and genetic data will be obtained and associated with neuroimaging data. Multimodal MRI will be used to examine distinct neurobiological traits, in particular by assessing regional gray and white matter volumes, covariance between gray matter volume in different regions, cortical thickness distribution, region-of-interest analyses and neural function during memory and response inhibition tasks and effective connectivity between regions.Expected Value of Proposed ProjectBrain structural and functional correlates of the at-risk mental state and first-episode subjects will advance our understanding of the mechanisms underlying the development of psychosis. Also, a better understanding of genetic influences on brain structure and function and structure-cognition associations of the brain will shed light on the neurobiological mechanisms that mediate contribution to key aspects of cognitive abnormalities in schizophrenia and its prodromal state. Determining the trajectory of structural and neural abnormalities will improve our knowledge of the neuronal circuits and cognitive processes that are implicated in biological vulnerability to mental illness. This may facilitate the identification of individuals at increased risk and improve clinical intervention to be targeted.
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