Type

Journal Article

Authors

D W Morris
A Corvin
M Gill
M C O'Donovan
M J Owen
K Mantripragada
A Richards
D Harold
D Cosgrove
S McCarthy-Jones
and 3 others

Subjects

Psychology

Topics
memory function temporal lobe component learning and memory brain expression complement activation major histocompatibility complex

Genetically predicted complement component 4A expression: effects on memory function and middle temporal lobe activation. (2018)

Abstract 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. 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. 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). 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.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

D W Morris, A Corvin, M Gill, M C O'Donovan, M J Owen, K Mantripragada, A Richards, D Harold, D Cosgrove, S McCarthy-Jones and 3 others

Experts in our system

1
Derrek Morris
Trinity College Dublin
Total Publications: 4
 
2
Aiden Corvin
Trinity College Dublin
Total Publications: 190
 
3
Michael Gill
Trinity College Dublin
Total Publications: 260
 
4
M C O'Donovan
Trinity College Dublin
Total Publications: 18
 
5
Michael J Owen
Royal College of Surgeons in Ireland
Total Publications: 19
 
6
Kiran Mantripragada
Dublin City University
Total Publications: 5
 
7
Alex Richards
Dublin City University
Total Publications: 6
 
8
Denise Harold
Dublin City University
Total Publications: 7
 
9
Donna Cosgrove
Dublin City University
Total Publications: 6
 
10
Simon McCarthy-Jones
Trinity College Dublin
Total Publications: 19