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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 拢25,000 in the coming academic financial year.

Successful applications for our small grants scheme 2021/2022

The IoMH have successfully awarded 2021/22聽Small Grants to fund three聽proposals that support interdisciplinary mental health research.

Disentangling Sensory and Genetic Risk Factors for Cortical Circuit Dysfunction聽in a Mouse Model of Schizophrenia

Lead applicants: Jennifer Linden, Elvira Bramon

顿别蝉肠谤颈辫迟颈辞苍:听Breakthroughs in mechanistic understanding of psychiatric diseases require insight into how聽experience and genetics interact to cause neural circuit dysfunction. Here, we seek to define how聽hearing impairment interacts with genetic risk for schizophrenia to affect excitation/inhibition聽balance in cortical circuits. Hearing impairment is a risk factor for psychotic experiences and聽schizophrenia, with odds ratios of 2-3 in meta-analysis of longitudinal studies. The biological聽mechanisms underlying this association remain poorly understood.

We hypothesise that hearing聽impairment can act as a 鈥渟econd hit鈥� for cortical circuit dysfunction in combination with genetic聽vulnerability to schizophrenia, by shifting cortical excitation/inhibition balance towards聽pathological excitation. We propose to test this hypothesis in the Df1/+ mouse model of human聽22q11.2 Deletion Syndrome, a chromosomal disorder which increases susceptibility to both聽schizophrenia and hearing impairment. We will compare cortical circuit function between 顿蹿1/+听mice with hearing impairment, Df1/+ mice without hearing impairment, and WT mice with or聽without experimentally induced hearing impairment. We will use high-density multi-electrodes聽(Neuropixels) to track neuronal population activity in the mouse auditory cortex with cellular-level聽spatial resolution and sub-millisecond temporal resolution, analysing how interactions between聽hearing impairment and genetic risk factors for schizophrenia affect spontaneous cortical activity,聽correlated firing among neurons, and other intracortical signs of excitation/inhibition imbalance.聽Additionally, we will seek to identify novel EEG measures of cortical excitation/inhibition聽imbalance in mice that could be used as biomarkers for cortical circuit dysfunction in patients.

Interoceptive iNsight and Metacognitive Efficacy beliefs- InMe:聽Developing and piloting a RCT protocol for a neurobiofeedback-assisted psychological聽intervention for eating and somatic symptom awareness

Lead applicants: Katerina Fotopoulou, Caroline Selai

顿别蝉肠谤颈辫迟颈辞苍:听Disruptions in interoception (the sensing, perception and interpretation of one鈥檚 physiological states)聽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聽interdisciplinary expertise required to identify and therapeutically target psychophysiological聽mechanisms has limited the efficacy of related therapeutic endeavours.

In this new interdisciplinary聽collaboration, we aim to combine the advantages of previous 鈥榖iofeedback鈥� interventions (e.g.聽using聽a wearable device to allow individuals to monitor their heartrate) and 鈥榤etacognitive鈥櫬�psychotherapies (i.e. addressing individuals鈥� beliefs about the meaning of physiological signals) for聽identifying the key mechanisms that contribute to the effective treatment of interoceptive聽dysfunctions and related mental health symptoms.聽Specifically, we aim to develop and test the efficacy and mechanisms of action of a novel,聽interdisciplinary (psychophysiological) therapeutic module (INME) to treat subclinical symptoms of聽disordered eating and somatisation. INME uses cardiac biofeedback during guided respiration聽exercises to train individuals to down-regulate their own heartrate under different conditions of聽stress, while also enhancing related metacognitive beliefs (the hypothesised primary pathogenic聽mechanism). We will aim to:

1. Develop and test a protocol for a pilot RCT testing the feasibility and efficacy of INME on treating聽subclinical symptoms of disordered eating and somatisation.
2. Form Public Patient Involvement (PPI) groups with patients recovered from eating, functional and聽somatic symptom disorders and expert clinicians, to inform all aspects of the research.
3. Use (1) and (2) to develop a protocol for a large, follow-up transdiagnostic RCT targeting key聽pathogenic mechanisms and feasible determinants of therapeutic change.

As most existing studies on the relationship between interoception and mental health are聽correlational, our intervention study may suggest clinical effects, as well as offer new insights about聽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

顿别蝉肠谤颈辫迟颈辞苍:听Problems in social functioning are not only a core element in the diagnosis and聽experience of schizophrenia, but also strongly debilitating, affecting the ability to work, to聽maintain relationships, and overall well-being. Changes in social function are also often the聽first sign of schizophrenia.聽There is no simple answer as to what causes schizophrenia. However, research has聽consistently shown that genetics is important. Very recently, a large collaboration of聽research teams, including the McQuillin team, identified specific changes in ten genes that聽greatly increase the risk of developing schizophrenia. While these changes are rare, further聽study of the function of these genes will help us better understand how schizophrenia聽causes its symptoms.聽

The Dreosti聽team has pioneered assays to detect subtle changes in social behaviour聽in young zebrafish and has developed protocols to study the anatomy and function of the聽underlying social circuit. While the Dreosti lab has shown how the assays can be聽successfully used to characterise the effects of social environment on social behaviour,聽other labs have recently used the same assay to show how a schizophrenia related gene聽NR3C2 can cause social behavioural changes. The Dreosti lab has now also developed聽genetic methods to rapidly generate zebrafish with genetic alterations, which can be used聽to validate the genes identified by the McQuillin lab. These experiments will be crucial in聽shedding light on the pathogenesis of schizophrenia and facilitating the design of future聽translational experiments.