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White Matter Neurobiology of Psychosis

Neuroimaging, Genetic and Imaging-Genetic Paradigms to Elucidate Brain White Matter Disruptions Underlying Major Psychoses

Schizophrenia (SZ) and bipolar disorder (BD) are two severe psychotic illnesses that can afflict up to 2-3% of the population worldwide. Given the enormity of the burden of disease and the extent of treatment resistance, the search for neurobiological bases of psychotic disorders has taken greater urgency. Current approaches include neuroimaging, genomic and molecular approaches.

Neuroimaging studies compare the structure and function of various brain regions of patients with normal controls to determine pathology in terms of specific brain volume differences, white matter disruptions, changes in glucose metabolism, functional activations during cognitive tasks, as well as brain chemical levels in vivo.

Genetic studies allow a better understanding of candidate genetic factors and functional pathways that may underlie the pathophysiology of psychotic conditions. When genetic approaches are combined with other approaches, such as neuroimaging strategies, they can be useful tools in highlighting brain changes that may be mediated by underlying genetic factors which are integral to neural structure and function, including neuronal organization, neuronal signaling and inter-neuronal communication. Up to more recently, most studies have examined the changes in brain grey matter in psychosis with less studies focusing on understanding white matter integrity changes.

Our research themes cover a series of inter-related projects:

  • Determination of brain white matter changes in SZ and BD using structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) and their relationship to psychotic phenomenology.
  • Understanding longitudinal changes of these brain white matter changes and their inter-relationships with neurocognitive functioning.
  • Elucidation of genetic factors underlying brain neuroanatomical changes and impact on functional outcomes. 

The projects and team members are supported by research funds totalling over S$1.2 million over the years, awarded by the National Medical Research Council (NMRC), Institutional Block Grant (IBG), National Healthcare Group (NHG), Agency for Science, Technology And Research, Ministry of Education (MOE) and the National University of Singapore.

Principal Investigator:

  • A/Prof Sim Kang, Institute of Mental Health


  • Prof Wieslaw Nowinski, Singapore Bioimaging Consortium, ASTAR
  • A/Prof Liu JianJun, Genome Institute of Singapore
  • Dr Sitoh Yih Yian, National Neuroscience Institute
  • Dr Jimmy Lee, Institute of Mental Health
  • A/Prof Qiu Anqi, National University of Singapore
  • Asst/Prof Steve Graham, National University of Singapore
  • A/Prof Simon Collinson, National University of Singapore
A member of National Healthcare Group ISO   Comm Chest Award Bronze