Neurobiology of Schizophrenia and Affective Disorder
The focus of the work is aimed at disentangling the neurobiological mechanisms leading to the development and manifestations of the major psychoses (schizophrenia, bipolar disorder, major depression) and understanding the evident overlap in clinical expression, genetic background and developmental antecedents of these. To do this we have been and continuing to:
· Establish a methodology for recruiting and assessing individuals who are at high risk of developing a major psychosis.
· Develop the use of cognitive phenotypes to investigate candidate genes in the major psychoses.
· Combine basic, methodological, and clinical studies using both PET and the MRI 3T human and 4.7T animal systems, to develop novel methods for indexing neurotransmitter release and drug action in the human brain. Clinical studies of in vivo neurochemistry, as well as involving established patient populations, will focus on individuals deemed to be ‘at risk’ of major depression and schizophrenia.
· Maintain collaborations with Dept Visual Neuroscience on a) use of oculomotor paradigms sensitive to cognitive dysfunction in psychosis and b) examination of whether abnormal rest/activity cycles in the psychoses reflect abnormal neurobiological mechanisms.
· Develop further the adaptation and development of methods for studying non-linear complex systems and apply the analytical methods to study of psychosis. Extend the application of the methods developed from EEG to high density EEG, MEG and DTI magnetic resonance imaging scanning.
Current projects
5-HT changes in psychiatric disease and following psychotrophic treatment.
PET investigations of serotonergic function in individuals deemed to be at risk of major depressive disorders.
A PET study of the dopaminergic system in depression.
A PET study of the 5-HT1A receptor in schizophrenia and its occupancy by antipsychotic drugs.
Use of Tyrosine depletion to assess the role of dopamine in major depression.
Cognitive dysfunction in first episode psychosis: differences between schizophrenia and bipolar disorder; effect of pre-morbid function and duration of untreated psychosis; relationship to outcome.
Longitudinal changes in cerebral structure using MTR and DTI MRI in first episode psychosis
Cerebral glutamate abnormalities in schizophrenia measured by 4.7T MRS
The nature of dysfunction of inhibitory processes in schizophrenia
Co-morbid substance abuse in first episode psychosis and effect on outcome
Insight and compliance in first episode schizophrenia: relationship to outcome.
Executive function as a predictor of outcome in alcoholism
The effect of conventional and atypical antipsychotic drugs on cognitive function in schizophrenia
Disturbances of circadian biology in schizophrenia
Study of glial cell number in the cingulated cortex in major affective illness.
Cingulate Cortex structure in Bipolar Disorder: an fMRI study.
