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Department of Psychology

Professor Robbins outlines the details of his Wellcome Trust Senior Investigator Award.


Wellcome Trust Senior Investigator Award : December 2014-February 2021.

£2.9M to support several post-doctoral positions and research expenses.

Summary

The overarching question is how impulsive-compulsive symptoms of psychiatric disorders such as obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD) and stimulant drug addiction can be understood in terms of common and distinctive aberrations of psychological processes arising from dysfunction of discrete neural systems including fronto-striatal-pallidal-thalamic loop circuits, and their chemical neuromodulation by neurotransmitters such as dopamine and serotonin. These systems are probably involved in virtually all neuropsychiatric syndromes but are associated with specific pathophysiology in the impulsive-compulsive disorders. One key hypothesis to be examined is the concept of imbalance in goal-directed and habit learning brain systems and how these systems are regulated by top-down control from the prefrontal cortex.

Ancillary questions are (i) to what extent impulsivity and compulsivity share overlapping neuropsychological mechanisms, inter-relate in different disorders, have different forms, and are affected by motivational/emotional state (e.g. anxiety). (ii) how new translational behavioural paradigms and neurobiological techniques can be used in rats and non-human primates to specify precise neural circuitry and psychological mechanisms causally underlying different forms of impulsivity and compulsivity, thereby identifying novel therapeutic interventions (drugs, behavioural therapy or deep brain stimulation).

Importance

The disproportionate socio-economic burden of mental health disorders in terms of government and research funding is well-known. The specific disorders targetted here in terms of DALY units and prevalence account together for a significant proportion of this burden. However, this research is important more generally for demonstrating the feasibility of integrating psychological constructs with (dys)functional neural circuits, cross-species, to provide candidate neurobehavioural endophenotypes with greater explanatory power for human pathophysiology than existing psychiatric nosology. By enhancing accuracy of diagnosis, such cross-cutting endophenotypes will result in more accurate phenotypes for psychiatric genetics, more homogeneous cohorts and sensitive measures for pharmaceutical trials, and potentially, early detection of vulnerability, allowing interventions before the disorders become chronic and relapsing. The studies will be highly relevant to the U.S. National Institute of Mental Health Initiative on Research Domain Criteria, replacing the traditional DSM approach to psychiatric nosology with a cognitive and behavioural neuroscientific oriented framework.

Techniques to be used

The experiments with animals will employ, amongst other techniques, innovative DREADDS technology (Designer Drugs Exclusively Activating Designer Receptors) which holds promise for specific identification of neural circuitry in control of discrete psychological functions. This may eventually lead to therapeutic applications in humans. The human work with patients and healthy volunteers will include a variety of brain imaging modalities including functional magnetic resonance imaging and resting state and functional connectivity studies, combined, where feasible, with and theoretically driven psychological paradigms and neuropsychological assessments.

Professor Trevor W. Robbins