Senior Research Fellow
The development of treatments for mood disorders
My interests are in the treatment of bipolar disorder and the application of neuroscience in understanding the neurobiology of mood disorders, with a focus on developing new treatments
Severe mood disorders are, or are becoming to be understood as, brain diseases. To improve our understanding of the impact of our treatments we need better ways of examining brain structure and function. Oxford provides a fantastic environment in which to achieve this using techniques like fMRI and MEG.
During my research training I made seminal discoveries on the mechanisms of kinaesthesia, the control of isometric contraction by muscle afferents and the role of the central command to exercise in the regulation of the cardiovascular and respiratory systems; this work is still still frequently cited 30 years after publication.
I made a biochemical and behavioural analysis of serotonin function at novel receptors in the brain and how it is modified by antidepressants and lithium: this had a lasting impact on how to screen for new antidepressants.
Translating my pharmacological interests into man, I initiated pharmacological dissection
of the processing of facial expression of emotion and memory. This may transform our understanding of how antidepressants work at a psychological level - by correcting unconscious biases in perception that are a key component of social cognition. This work has implications for how we should screen putative antidepressants in human volunteers and so potentially facilitate drug discovery early in Phase I development.
I have made fundamental observations on the functional and structural brain changes associated with severe depression. This has implications for how we should classify the disease. The findings in very chronic depression showed loss of tissue in hippocampus that correlated with memory impairment. This has supported a shift in drug development towards an interest in neurogenesis as a mechanism underlying the action of effective antidepressants and cognition as a target for remediation in depression.
I have contributed to the systematic review of most of the important medical treatments of bipolar disorder. and, with others, wrote widely cited guidelines supporting evidence-based treatment. I have been a lead investigator in clinical trials for bipolar affective disorder, including the BALANCE, CEQUEL and OXTEXT studies.
Mood disorders are highly recurrent illnesses. Therefore, one important research strategy that I
have supported in my department involves the identification of risk factors for relapsing illness that might form targets for prevention. I believe developments in the cognitive neuropsychology of emotion provide a fruitful starting point for defining the phenotype in mood disorder more precisely and without clinical bias. An improved theoretical framework could move us beyond the simple phenomenology that still dominates approaches to aetiology. Relevant neurocognitive mechanisms and their supporting brain networks can inform the dimensional approach that the problem clearly merits. In addition, it offers the potential for a subsequent dissection on the basis of brain connectivity, neurotransmitter function and gene expression. It may also offer much needed assays for the actions of new medicines or for psychological treatments: ‘experimental medicine’ has been identified is the key mission for academic medicine in this country and I am strongly committed to it.