Medial temporal lobe function and associative memory formation in schizophrenia

Schizophrenia is a common and severe psychiatric illness. Our work aims to understand more about the causes of this illness.
Recent studies have identified genes that are associated with risk for schizophrenia. These genes affect the cellular processes underlying learning and memory. We believe that alterations in simple learning processes can result in many of the problems seen in schizophrenia. We are therefore investigating how patients with schizophrenia and their relatives perform on basic learning tasks. We are also looking at their brain activity while carrying out these learning tasks using safe magentic resonance imaging (MRI) scanning technology to see if there are differences in brain activity between people with schizophrenia and healthy control participants.
We are in addition directly investigating how specific genes associated with schizophrenia, such as a gene called Neuregulin-1, cause the illness. In particular we are studying the effects that these genes have on brain structure and function as well as on learning processes and the development of symptoms.
We hope that understanding more about the basic causes of schizophrenia will eventually enable entirely novel treatments to be developed for this disabling mental health illness.

Schizophrenia is a common and severe neuro-psychiatric disorder. One of the characteristic abnormalities in brain structure seen in schizophrenia is a reduction in volume of the medial temporal lobe (MTL). Reductions in MTL volume is also seen in the unaffected relatives of schizophrenic patients, suggesting that this may reflect genetic risk for the disorder. The MTL is required for associative learning underlying the formation of episodic and emotional memories, areas in which patients with schizophrenia show marked deficits. Schizophrenia susceptibility genes, such as Neuregulin-1 (NRG1) show convergent effects on molecular processes underlying associative memory formation. Furthermore studies in the local population have recently identified common variants in NRG1 associated with increased risk for schizophrenia. In this project I aim to:

(i) Investigate the performance of patients with schizophrenia and their first degree relatives in two behavioural tests of associative memory formation: face-name pair memory and Pavlovian conditioning.
(ii) Use functional magnetic imaging to investigate the activation of the MTL in patients and relatives performing these associative memory tasks.
(iii) Determine the impact of genetic variants in NRG1 on associative memory formation and MTL structure and activation.

These studies will directly investigate the basic neurobiological process of associative memory formation in schizophrenia, and will develop models in which to test the impact of genes conferring susceptibility to schizophrenia on associative memory formation. In addition this work will provide me with extensive training in the areas of functional imaging and psychiatric genetics.