{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T05:31:05Z","timestamp":1794375065002,"version":"4.9.0"},"reference-count":35,"publisher":"Cambridge University Press (CUP)","issue":"10","license":[{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0033291717002987_sec_a1\"><jats:title>Background<\/jats:title><jats:p>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 (<jats:italic>C4<\/jats:italic>) gene. This structural variation generates varying levels of <jats:italic>C4<\/jats:italic> RNA expression, and genetic information from the MHC region can now be used to predict <jats:italic>C4<\/jats:italic> RNA expression in the brain. Increased predicted <jats:italic>C4A<\/jats:italic> RNA expression is associated with the risk of SZ, and <jats:italic>C4<\/jats:italic> is reported to influence synaptic pruning in animal models.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291717002987_sec_a2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted <jats:italic>C4A<\/jats:italic> RNA expression was associated with reduced memory function in a large (<jats:italic>n<\/jats:italic> = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291717002987_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>We observed that increased predicted <jats:italic>C4A<\/jats:italic> RNA expression predicted poorer performance on measures of memory recall (<jats:italic>p<\/jats:italic> = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted <jats:italic>C4A<\/jats:italic> RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (<jats:italic>p<\/jats:italic> &lt; 0.05, corrected).<\/jats:p><\/jats:sec><jats:sec id=\"S0033291717002987_sec_a4\" sec-type=\"conclusion\"><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that the effects of <jats:italic>C4<\/jats:italic> 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 <jats:italic>C4<\/jats:italic>\u2019s developmental role.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291717002987","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T19:54:40Z","timestamp":1515527680000},"page":"1608-1615","source":"Crossref","is-referenced-by-count":37,"title":["Genetically predicted complement component 4A expression: effects on memory function and middle temporal lobe activation"],"prefix":"10.1017","volume":"48","author":[{"given":"G.","family":"Donohoe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Mothersill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"McCarthy-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Cosgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Harold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Mantripragada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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