Leeds Psychosis Research Group

What we do

The Leeds Psychosis Research Group is a cross-faculty, multidisciplinary team which aims to understand the causes of schizophrenia, other forms of psychosis and intellectual disability. Our researchers have skills that span synaptic physiology and behaviour in preclinical models, through modern high-powered genetics and molecular biology approaches. The team also includes clinicians working with families affected by schizophrenia, other mental health problems or intellectual disability. Our group undertakes studies in brain imaging, clinical research and animal model development, with the aim of identifying what mechanisms are contributing to intellectual disability and schiozophrenia at the neuronal and cellular level. The outcome of our work will be a greater understanding of the basis of psychosis and/or intellectual disability, so that ultimately we may be able to contribute to the development of new and better treatments for those affected by these disorders.

Much of our current research focuses on conditions affecting the brain that have a strong genetic component. To inform understanding of aetiology, we are using next generation sequencing and transcriptome analyses to identify potentially causative genetic mutations in multiplex families from populations that are both highly consanguineous (due to cousin marriage), increasing the frequency of all recessive disease, and endogamous, potentially reducing genetic complexity. Our approaches also include the use of cellular models and genetically-altered animals to explore disease mechanisms and novel treatments. Cognitive endophenotypes such as working memory and executive function have also been studied by the group in patients with schizophrenia and other psychoses. We have explored the relationship between the neural correlates of performing these tasks and patients’ and their at-risk relatives’ genetic makeup. In a collaboration with Professors Peter Wooduff and Iain Wilkinson at Sheffield University, we carried out functional magnetic resonance imaging in patients with schizophrenia and their unaffected relatives. We are also collaborating with Dr Hassen Al-Amin and Dr Suhaila Ghuloum from Weill Cornell University in Doha, studying a cohort of Qatari patients with schizophrenia.

Funding

Our work is funded by the Medical Research Council and the Qatari National Research Fund.

Key publications

1. The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress. Klaus K, Butler K, Durrant SJ, Ali M, Inglehearn CF, Hodgson TL, Gutierrez H, Pennington K. Brain Behav. 2017 Apr 12;7(5):e00695. doi: 10.1002/brb3.695.
    
2. Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family. Al-Amri A, Saegh AA, Al-Mamari W, El-Asrag ME, Ivorra JL, Cardno AG, Inglehearn CF, Clapcote SJ, Ali M. Am J Med Genet A. 2016 Jul;170(7):1826-31.
    
3. Heimler Syndrome is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. Ratbi I, Falkenberg KD, Sommen M, Al-Sheqaih N, Guaoua S, Vandeweyer G, Urquhart JE, Chandler KE, Williams SG, Roberts NA, El Alloussi M, Black GC, Ferdinandusse S, Ramdi H, Heimler A, Fryer A, Lynch SA, Cooper N, Ong KR, Smith CE, Inglehearn CF, Mighell AJ, Elcock C, Poulter JA, Tischkowitz M, Davies SJ, Sefiani A, Mironov AA, Newman WG, Waterham HR, Van Camp G. Am J Hum Genet. 2015 Oct 1;97(4):535-45.

Who we are

People

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