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Genetically predicted complement component 4A expression: effects on memory function and middle temporal lobe activation

Donohoe, Gary, Holland, Jessica, Mothersill, David, McCarthy-Jones, Simon, Cosgrove, Donna, Harold, Denise, Richards, Alexander, Mantripragada, Kiran, Owen, Michael J., O'Donovan, Michael C., Gill, Michael, Corvin, Aiden and Morris, Derek W. (2018) Genetically predicted complement component 4A expression: effects on memory function and middle temporal lobe activation. Psychological Medicine, 48 (10). pp. 1608-1615. ISSN 1469-8978

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Official URL: http://dx.doi.org/10.1017/S0033291717002987

Abstract

Background
The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.

Methods
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.

Results
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).

Conclusions
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.

Item Type: Article
Subjects: B Philosophy. Psychology. Religion > Psychology
B Philosophy. Psychology. Religion > Psychology > Cognitive psychology
Divisions: School of Business > Staff Research and Publications
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Depositing User: CAOIMHE NI MHAICIN
Date Deposited: 20 Apr 2020 09:32
Last Modified: 20 Apr 2020 09:32
URI: http://trap.ncirl.ie/id/eprint/4188

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