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Uncovering brain circuit pathologies in schizophrenia

Polygenetics of attention and effort

About the project

Schizophrenia is a severe mental disorder with high morbidity, large impact on patients and their families, and huge costs for society and the health care sector globally. Despite progress in genetic, brain imaging, and cognitive research, the biological deficiencies underlying schizophrenia are still mainly unknown. Cognitive abnormalities are key components of schizophrenia, and unlike positive symptoms, including hallucinations and delusions, cognitive symptoms predate diagnosis, predict functional out come, resist treatment, and often persist throughout life. Understanding the biological basis of cognitive abnormalities in schizophrenia, at molecular and brain network levels, will be critically important for the development of treatments that can ameli orate them. There is strong evidence for a role of brain neuromodulatory systems in attention and learning, especially involving noradrenaline, acetylcholine, and dopamine, but their interaction patterns are less well understood.

Objectives

We hypothesize that an important basis of cognitive symptoms in schizophrenia is abnormalities in the brainstem noradrenergic system, and particularly its interaction with dopamine systems and brain control networks. We will take advantage of recent methodological advances to uncover brain circuit malfunctions underlying cognitive abnormalities in schizophrenia. In particular, we will combine new methods from large-scale genetics research with measurements of task-dependent pupil dilations and functional imaging of brain networks that underlie flexible goal-directed behavior.

We aim to define a genetic signal that is specific to the biological deficiencies that underlie schizophrenia. Subsequently, we will investigate where in the brain, and when in development, from fetal stages to adulthood, these genetic markers are particularly active.

Financing

The Research Council of Norway (FRIMEDBIO - Young talented researchers) 2014 - 2018.

Published Oct. 24, 2016 12:08 PM