17 September 2019

Are memory impairments in early and chronic schizophrenia related to the volume of particular hippocampal subfields?

Can you tell us more about yourself?

I’m a final year PhD student at the Melbourne Neuropsychiatry Centre, University of Melbourne. The core research focus of our lab is understanding the neurobiology of psychosis and other disorders, such as autism, depression, and anxiety. My own PhD research has focused on the interaction between brain structure and cognitive impairment, particularly memory impairment, across different stages of psychotic illness.

What is the rationale behind your study?

Individuals with schizophrenia often present with quite substantial memory deficits, and these deficits have been shown to be a strong predictor of functional impairment in schizophrenia.

A number of previous studies have investigated the role of the hippocampus in memory impairment in schizophrenia, and have tended to find that smaller hippocampi mean worse memory performance in both early and chronic schizophrenia. However, we now know that the hippocampus isn’t a uniform structure but rather is made up of several functionally distinct subfields, and volume loss appears to spread across these subfields as psychotic illness progresses.

Our study therefore aimed to investigate whether memory impairment in early and chronic schizophrenia was related to the volume of particular hippocampal subfields. The ability to pinpoint which subfields are implicated in memory impairments could provide us with clues as to the mechanisms that might be driving these impairments in the disorder.

Which methods did you use?

We obtained magnetic resonance imaging (MRI) scans from 4 groups of people: 52 individuals with chronic schizophrenia, 28 youth with recent-onset psychosis, 52 older healthy controls, and 28 younger healthy controls. We were then able to use a program called MAGeT Brain to segment the hippocampi into five subfields (CA1, CA2/CA3, CA4/dentate gyrus, stratum, subiculum) in each hemisphere. Each participant also completed the CANTAB Paired Associates Learning (PAL) task so we could measure their episodic memory ability.

What were your key study findings?

Our key findings were that, in both patient groups, there were relationships between PAL performance and hippocampal subfield volumes that weren’t observed in the healthy control groups. In particular, smaller CA4/dentate gyrus and stratum volumes were associated with poorer performance on the PAL task in patients.

What are the implications of your research?

These findings are important because by identifying the particular hippocampal subfields implicated in episodic memory impairments in schizophrenia, we move one step closer to understanding the neuropathology that might cause these deficits. For example, the dentate gyrus relies heavily on the neurotransmitter glutamate to function, and numerous studies suggest that glutamate systems are disrupted in schizophrenia. Therefore, could targeting these systems help to improve memory functioning in the disorder?

Why did you choose CANTAB for your study?

We chose CANTAB because the portable, touch-screen technology made administering a cognitive battery to our participants easy when we travelled off-site to the hospital. Previous studies, particularly in Alzheimer’s disease, have also shown that the CANTAB PAL task is an extremely sensitive measure of memory impairments and is related to hippocampal function, which, of course, were very important factors in the current study.

What are the future areas of investigation that could follow your research?

Longitudinal studies that track relationships between memory performance and hippocampal subfield volumes over time would be particularly valuable given that we found relationships in different hemispheres in recent-onset and chronic schizophrenia. Determining whether drugs that act on glutamate pathways also improve memory performance in schizophrenia would also be an exciting next step.

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Cassandra Wannan

University of Melbourne

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