The basis of psychosis; from the genetic causes to improved therapeutics

The core function of our group is to use our multidisciplinary backgrounds to understand the genetic factors that influence the onset of psychiatric disorders. Thus, one of our primary tasks is to work with afflicted families to identify the genes associated with these disorders. We are particularly interested in how these genes result in the abnormal behaviours that are primarily used to diagnose the psychiatric condition. To understand this, our group undertakes studies in brain imaging, clinical research and animal model development, with an aim to identify on the neuronal and cellular level what mechanisms are contributing to the disorder. The outcome of our work is to understand the basis of psychosis so that we can develop new ways of identifying and preventing it, and generating new treatments for those afflicted with these disorders.

The genetic basis of schizophrenia within families

Our current research is focussed on psychiatric conditions that have a strong genetic component, such as bipolar disorder and schizophrenia. These conditions are inadequately treated by currently available medications, but our ultimate aim is to develop improved therapies. To inform understanding of aetiology, we are using next generation sequencing 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 approach then uses cell cultures and genetically-altered mice to explore disease mechanisms and novel treatments.

The role of neurexins in synaptic physiology

Neurexins have recently been identified as genes that are associated with Schizophrenia and autism spectrum disorders. Research led by Dr. Dachtler and Dr. Clapcote aims to discover how alterations to the neurexin genes in mouse models may result in behaviours associated with these disorders. Dr. Dachtler aims to discover how these genetic alterations affect synaptic function using electrophysiological approaches, from the single neurone level through to awake-behaving network activity.

Neural underpinnings of working memory processes in familial schizophrenia

Cognitive endophenotypes such as working memory and executive function have been extensively studied in patients with schizophrenia. However the relationship between the neural correlates of performing these tasks and patients’ and their at-risk relatives’ genetic makeup have not yet been adequately explored. Dr Tariq Mahmood in collaboration with Professor Peter Wooduff’s SCANLab at Sheffield University is carrying out functional magnetic resonance imaging in patients and their unaffected homozygous and heterozygous relatives. Preliminary findings were presented at the Royal college of Psychiatrists International Congress 2014.