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

G Donohoe1, J Holland1, D Mothersill1

  • 1The Cognitive Genetics & Cognitive Therapy Group,The School of Psychology and Discipline of Biochemistry,The Centre for Neuroimaging & Cognitive Genomics,National University of Ireland Galway,University Road,Galway,Ireland.

Psychological Medicine
|January 10, 2018
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Summary
This summary is machine-generated.

Increased complement component 4A (C4A) RNA expression is linked to poorer memory and reduced brain activity in healthy individuals, suggesting a mechanism for schizophrenia risk.

Keywords:
Complement component 4MHC complexmemory functionschizophreniatemporal cortex

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • The major histocompatibility complex (MHC) locus is associated with schizophrenia (SZ) risk.
  • Structural variation in the complement component 4 (C4) gene partially explains this association.
  • Higher C4A RNA expression in the brain is linked to increased SZ risk and influences synaptic pruning.

Purpose of the Study:

  • To investigate the association between predicted C4A RNA expression and memory function in psychosis cases and healthy individuals.
  • To examine the relationship between predicted C4A RNA expression and cortical activation during cognitive tasks.

Main Methods:

  • Utilized a large dataset (n=1238) of psychosis cases and healthy participants.
  • Assessed memory recall performance and task-dependent cortical activation.
  • Predicted C4A RNA expression based on genetic information from the MHC region.

Main Results:

  • Increased predicted C4A RNA expression was significantly associated with poorer memory recall (p=0.016).
  • In healthy participants, higher predicted C4A RNA expression correlated with reduced middle temporal cortex activity during visual processing (p<0.05).

Conclusions:

  • C4 influences cognition at both behavioral and cortical levels, potentially mediating illness risk.
  • Memory and learning deficits linked to C4 may offer therapeutic targets for novel molecular interventions.