{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:14:53Z","timestamp":1780560893996,"version":"3.54.1"},"posted":{"date-parts":[[2023,6,14]]},"group-title":"Neuroscience","reference-count":126,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modelling of post-synaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD). We combined our model with data from post-mortem mRNA expression studies (CommonMind gene-expression datasets) to assess the consequences of altered expression of plasticity-regulating genes for the amplitude of LTP and LTD. Our results show that the expression alterations observed\n                  <jats:italic>post mortem<\/jats:italic>\n                  , especially those in anterior cingulate cortex, lead to impaired PKA-pathway-mediated LTP in synapses containing GluR1 receptors. We validated these findings using a genotyped EEG dataset where polygenic risk scores for synaptic and ion channel-encoding genes as well as modulation of visual evoked potentials (VEP) were determined for 286 healthy controls. Our results provide a possible genetic mechanism for plasticity impairments in schizophrenia, which can lead to improved understanding and, ultimately, treatment of the disorder.\n                <\/jats:p>","DOI":"10.1101\/2023.06.14.544920","type":"posted-content","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T10:55:11Z","timestamp":1686740111000},"source":"Crossref","is-referenced-by-count":1,"title":["Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modelling"],"prefix":"10.64898","author":[{"given":"Tuomo","family":"M\u00e4aki-Marttunen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim T.","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Akkouh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Shadrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Valstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobj\u00f8rn","family":"Elvs\u00e5ashagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja-Leena","family":"Linne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srdjan","family":"Djurovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaute T.","family":"Einevoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-3568","authenticated-orcid":false,"given":"Ole A.","family":"Andreassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"30","key":"2023061700300849000_2023.06.14.544920v1.1","first-page":"12347","article-title":"Araya, R., Nikolenko, V., Eisenthal, K. 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Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue. PLoS genetics, 14(8):e1007607.","DOI":"10.1371\/journal.pgen.1007607"},{"key":"2023061700300849000_2023.06.14.544920v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5400.381"},{"key":"2023061700300849000_2023.06.14.544920v1.6","doi-asserted-by":"crossref","unstructured":"[Billingsley, et al., 2018] Billingsley, K. J., Manca, M., Gianfrancesco, O., Collier, D. A., Sharp, H., Bubb, V. J., and Quinn, J. P. (2018). Regulatory characterisation of the schizophrenia-associated cacna1c proximal promoter and the potential role for the transcription factor ezh2 in schizophrenia aetiology. Schizophrenia research, 199:168\u2013175.","DOI":"10.1016\/j.schres.2018.02.036"},{"key":"2023061700300849000_2023.06.14.544920v1.7","doi-asserted-by":"crossref","unstructured":"[Blackwell, et al., 2018] Blackwell, K. T., Salinas, A. 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