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As part of its commitment to support mental health research, the IoMH has established a small grants scheme and is pleased to announce awards totalling £25,000 in the coming academic financial year.
Successful applications for our small grants scheme 2021/2022
The IoMH have successfully awarded 2021/22 Small Grants to fund three proposals that support interdisciplinary mental health research.
Disentangling Sensory and Genetic Risk Factors for Cortical Circuit Dysfunction in a Mouse Model of Schizophrenia
Lead applicants: Jennifer Linden, Elvira Bramon
Description: Breakthroughs in mechanistic understanding of psychiatric diseases require insight into how experience and genetics interact to cause neural circuit dysfunction. Here, we seek to define how hearing impairment interacts with genetic risk for schizophrenia to affect excitation/inhibition balance in cortical circuits. Hearing impairment is a risk factor for psychotic experiences and schizophrenia, with odds ratios of 2-3 in meta-analysis of longitudinal studies. The biological mechanisms underlying this association remain poorly understood.
We hypothesise that hearing impairment can act as a “second hit” for cortical circuit dysfunction in combination with genetic vulnerability to schizophrenia, by shifting cortical excitation/inhibition balance towards pathological excitation. We propose to test this hypothesis in the Df1/+ mouse model of human 22q11.2 Deletion Syndrome, a chromosomal disorder which increases susceptibility to both schizophrenia and hearing impairment. We will compare cortical circuit function between Df1/+ mice with hearing impairment, Df1/+ mice without hearing impairment, and WT mice with or without experimentally induced hearing impairment. We will use high-density multi-electrodes (Neuropixels) to track neuronal population activity in the mouse auditory cortex with cellular-level spatial resolution and sub-millisecond temporal resolution, analysing how interactions between hearing impairment and genetic risk factors for schizophrenia affect spontaneous cortical activity, correlated firing among neurons, and other intracortical signs of excitation/inhibition imbalance. Additionally, we will seek to identify novel EEG measures of cortical excitation/inhibition imbalance in mice that could be used as biomarkers for cortical circuit dysfunction in patients.
Interoceptive iNsight and Metacognitive Efficacy beliefs- InMe: Developing and piloting a RCT protocol for a neurobiofeedback-assisted psychological intervention for eating and somatic symptom awareness
Lead applicants: Katerina Fotopoulou, Caroline Selai
Description: Disruptions in interoception (the sensing, perception and interpretation of one’s physiological states) have emerged as a transdiagnostic pathogenic mechanism for several disorders at the mental/physical/health interface, such as eating, functional or somatic symptom disorders. However, the interdisciplinary expertise required to identify and therapeutically target psychophysiological mechanisms has limited the efficacy of related therapeutic endeavours.
In this new interdisciplinary collaboration, we aim to combine the advantages of previous ‘biofeedback’ interventions (e.g. using a wearable device to allow individuals to monitor their heartrate) and ‘metacognitive’ psychotherapies (i.e. addressing individuals’ beliefs about the meaning of physiological signals) for identifying the key mechanisms that contribute to the effective treatment of interoceptive dysfunctions and related mental health symptoms. Specifically, we aim to develop and test the efficacy and mechanisms of action of a novel, interdisciplinary (psychophysiological) therapeutic module (INME) to treat subclinical symptoms of disordered eating and somatisation. INME uses cardiac biofeedback during guided respiration exercises to train individuals to down-regulate their own heartrate under different conditions of stress, while also enhancing related metacognitive beliefs (the hypothesised primary pathogenic mechanism). We will aim to:
- Develop and test a protocol for a pilot RCT testing the feasibility and efficacy of INME on treating subclinical symptoms of disordered eating and somatisation.
- Form Public Patient Involvement (PPI) groups with patients recovered from eating, functional and somatic symptom disorders and expert clinicians, to inform all aspects of the research.
- Use (1) and (2) to develop a protocol for a large, follow-up transdiagnostic RCT targeting key pathogenic mechanisms and feasible determinants of therapeutic change.
As most existing studies on the relationship between interoception and mental health are correlational, our intervention study may suggest clinical effects, as well as offer new insights about the causal relationship between interoception and mental health.
Modelling the impact of schizophrenia risk variants on social behaviour in zebrafish
Lead applicants: Tom Ryan, Andrew McQuillin
Description: Problems in social functioning are not only a core element in the diagnosis and experience of schizophrenia, but also strongly debilitating, affecting the ability to work, to maintain relationships, and overall well-being. Changes in social function are also often the first sign of schizophrenia. There is no simple answer as to what causes schizophrenia. However, research has consistently shown that genetics is important. Very recently, a large collaboration of research teams, including the McQuillin team, identified specific changes in ten genes that greatly increase the risk of developing schizophrenia. While these changes are rare, further study of the function of these genes will help us better understand how schizophrenia causes its symptoms.
The Dreosti team has pioneered assays to detect subtle changes in social behaviour in young zebrafish and has developed protocols to study the anatomy and function of the underlying social circuit. While the Dreosti lab has shown how the assays can be successfully used to characterise the effects of social environment on social behaviour, other labs have recently used the same assay to show how a schizophrenia related gene NR3C2 can cause social behavioural changes. The Dreosti lab has now also developed genetic methods to rapidly generate zebrafish with genetic alterations, which can be used to validate the genes identified by the McQuillin lab. These experiments will be crucial in shedding light on the pathogenesis of schizophrenia and facilitating the design of future translational experiments.