Developing a test battery for evaluating treatment effects on emotional, motivational and social function in neuropsychiatry

People with mental health problems have profound emotional, motivational and social difficulties which dramatically affect their everyday function and wellbeing. Not only do these problems cause great distress to patients and their families, but also they act as a barrier to recovery and thus represent a significant social and economic burden. Despite the obvious importance of emotional and social functions, there is no accepted way of measuring them both objectively and comprehensively. Treatments for mental health problems, both drugs and "talking therapies", aim to improve emotional and social cognition and we therefore need good objective measures of these functions to assess how well new treatments are working. Objective measures of emotional, motivational and social function may predict how people will respond to different treatments (drugs or "talking therapies") and greatly improve the accuracy of clinical trials. When different studies use different measures, it can be difficult to draw conclusions across studies and we therefore make slower progress in terms of understanding and treating debilitating mental health problems. For these reasons, we will develop a standard set of measures of emotional and social function that can be used in future treatment trials and research studies, allowing meaningful comparisons between trials that lead to more accurate conclusions. Important aspects of function to assess include: how people respond to facial expressions of emotion; how they process positive and negative information; how they respond to incentives; whether they are motivated; whether they can exert self-control; and how they understand and interact with other people. For example, people with depression tend to interpret events more negatively, whereas people with schizophrenia tend to have difficulty understanding other people's emotions and intentions. To check that the tests can detect such important differences in function, we will test a large number of healthy people using these measures. To check that the tests are consistent and reliable, which is important in clinical trials, we will test some of these people on a second occasion. Developing standard and reliable tests will help to improve our evaluation of the most effective treatments for individuals with these disorders.

Emotional, motivational and social impairments are increasingly thought to be fundamental to the pathology of psychiatric disorders. Therefore any comprehensive assessment of neuropsychiatric patients should include measures of these aspects of behaviour. However, in contrast to measures of non-affective aspects of cognition via neuropsychological assessment, standardised and well-validated tests of affective functions are lacking, limiting the scope of clinical trials and hampering scientific progress. Well-designed, carefully validated and widely accepted measures of a comprehensive range of affective functions would facilitate clinical trials, both of drugs and psychological therapies which particularly aim to target emotional, motivational and social processes. Characterising deficits in these processes systematically across studies would also contribute to the definition of endophenotypes relevant to neuropsychiatric disorders with implications for understanding aetiology. In this proposal, we seek to develop a computerised battery comprising tests of emotional, motivational and social function. The battery will be optimised for use in clinical trials and multi-centre studies. Having developed and piloted a set of tests, we will then validate this battery in a group of 200 young, healthy volunteers and determine test-retest reliability by follow-up testing of 40 of the volunteers. Establishing reliability is critical to confirm the utility of the battery in longitudinal contexts such as clinical trials.

Mental ill-health is more widespread than many realise, with 16% of adults having a common mental health disorder at any one time (1) and up to 10% of children having a clinically diagnosable mental health problem which can often persist into adulthood (2). Emotional, social and motivational problems are important features of neuropsychiatric disorders, predicting long-term functional outcome. For example, emotional impairments are important determinants of functional outcome in psychosis and although current antipsychotic drugs have mood stabilizing properties, they have little impact on emotional impairments (3). Poor functional outcome in many disorders critically contributes to the social and economic burden of mental illness worldwide. The World Health Organisation estimates that 15% of the global burden of disease is attributable to mental health, with depression one of the leading causes of disability. In the UK alone the Sainsbury Centre for Mental Health has estimated the health, social and economic cost of mental health problems at £77 billion each year (4). Emotional, social and motivational problems are also significant features of neurodegenerative and other medical disorders contributing to their social and economic burden. Furthermore, these problems affect long term prognosis in a range of serious and chronic conditions, including cancer and cardiovascular disease. In order to reduce the burden of mental ill-health and to ensure individuals and society flourish, the MRC Review of Mental Health Research (5) stressed the importance of promoting new methodologies and innovations. Despite the importance of emotional, social and motivational functions, there is a lack of widely accepted, objective and standardised measures for comprehensive assessment of impairment profiles. Development of an innovative and objective battery, as proposed here, will therefore address an unmet need in translational research (Cooksey Gap 1), complementing standard clinical rating scale assessments. The battery will facilitate clinical trials of both pharmacological and non-pharmacological treatments. The difficulties many pharmaceutical companies have been experiencing with failed Phase 3 trials may be put down in part to heteroegeneity in clinical samples but also in part due to insensitive dependent variables, which this test battery could potentially help to circumvent. Furthermore, the battery will be an important tool for biomarker development and will facilitate research into mechanisms of psychiatric symptoms as well as characterisation of neuropsychiatrically relevant endophenotypes. If successful, the battery may have commercial value, given the relative success of cognitive test batteries. Thus the battery we propose to develop has a critical role in improving clinical trials, evaluating the impact of effective treatment and management aimed at improving functional outcomes in people with a range of mental health problems. It will also have utility in innovative research, including identification of endophenotypes, and in facilitating the prompt detection of 'high risk states' across the life course. (1) Beddington et al 2008 Nature, 455, 1057-1060 (2) Green, McGinnity, Meltzer et al 2005 Mental health of children and young people in Great Britain. Basingstoke, Hampshire UK. (3) Scoriels et al (2010, in press) Effects of modafinil on emotional functions in early psychosis.Biological Psychiatry. (4) Sainsbury Centre for Mental Health. Economic and Social Costs of Mental Illness in England. June 2003. (5) MRC Review of Mental Health Research: Report of the Strategic Review Group (2010)