{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:17:21Z","timestamp":1771611441193,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple genes within the DISC1 (Disrupted-in-Schizophrenia-1) interactome have been implicated in psychotic disorders, which are characterized by hallucinations, delusions, negative symptoms, and disorganized behavior. However, the genetic associations of specific psychotic symptoms remain poorly understood. Methods: We conducted a genetic association analysis of the DISC1 interactome for hallucinations and delusions in schizophrenia and bipolar disorder, using single-nucleotide polymorphism (SNP), gene, and gene-set approaches. Results: Our findings showed an association between the SNP rs6754640 in the NRXN1 gene and auditory hallucinations. Additionally, rs10263196 (EXOC4), rs7076156 (ZNF365), and nine NRXN1 SNPs were associated with delusions of reference, while rs17039676 (NRXN1) was linked to persecutory delusions. At the gene level, NRG1 and PCM1 were related to auditory hallucinations. The NRXN1, APP, EXOC4, and NUP210 genes were associated with delusions of reference, whereas NRG1 and APP were linked to persecutory delusions. Gene-set analysis indicated that pathways related to the regulation of neuronal structure and function were involved in auditory hallucinations, while cellular transport regulation pathways were associated with persecutory delusions. Conclusions: This study emphasizes the polygenic architecture of psychosis and suggests that distinct molecular mechanisms contribute to different types of hallucinations and delusions.<\/jats:p>","DOI":"10.3390\/ijms26178738","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Association of the DISC1 Interactome in Hallucinations and Delusions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9938-6139","authenticated-orcid":false,"given":"Araceli","family":"Guti\u00e9rrez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Laboratorio de Gen\u00f3mica de Enfermedades Psiqui\u00e1tricas y Neurodegenerativas, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Unidad de Posgrado, Edificio D, 1\u00b0 Piso, Circuito de Posgrados, Ciudad Universitaria, Alcald\u00eda Coyoac\u00e1n, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma Delia","family":"Genis-Mendoza","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica de Enfermedades Psiqui\u00e1tricas y Neurodegenerativas, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"},{"name":"Servicios de Atenci\u00f3n Psiqui\u00e1trica, Hospital Psiqui\u00e1trico Infantil \u201cJuan N. Navarro\u201d, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2537-858X","authenticated-orcid":false,"given":"Jorge Ameth","family":"Villatoro-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Unidad de An\u00e1lisis de Datos y Encuestas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-0752","authenticated-orcid":false,"given":"Mar\u00eda Elena","family":"Medina-Mora","sequence":"additional","affiliation":[{"name":"Unidad de An\u00e1lisis de Datos y Encuestas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-0067","authenticated-orcid":false,"given":"Humberto","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica de Enfermedades Psiqui\u00e1tricas y Neurodegenerativas, Instituto Nacional de Medicina Gen\u00f3mica, Ciudad de M\u00e9xico 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134754","DOI":"10.1016\/j.neulet.2020.134754","article-title":"Genetic variants associated with psychotic symptoms across psychiatric disorders","volume":"720","author":"Porcelli","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1038\/mp.2017.115","article-title":"Rare disruptive variants in the DISC1 Interactome and Regulome: Association with cognitive ability and schizophrenia","volume":"23","author":"Teng","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.biopsych.2018.05.009","article-title":"Endogenous cell type-specific Disrupted in Schizophrenia 1 interactomes reveal protein networks associated with neurodevelopmental disorders","volume":"85","author":"Wilkinson","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Facal, F., and Costas, J. (2019). Evidence of association of the DISC1 interactome gene set with schizophrenia from GWAS. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 95.","DOI":"10.1016\/j.pnpbp.2019.109729"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0140-6736(21)01730-X","article-title":"Schizophrenia","volume":"399","author":"Jauhar","year":"2022","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/bdi.12527","article-title":"Psychosis in bipolar disorder: Does it represent a more \u201csevere\u201d illness?","volume":"20","author":"Burton","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/schbul\/sbu016","article-title":"Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder","volume":"40","author":"Cardno","year":"2014","journal-title":"Schizophr. Bull."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1176\/appi.ajp.2020.20020162","article-title":"Psychotic experiences, cognitive decline, and genetic vulnerabilities in relation to developing psychotic disorders","volume":"177","author":"Kalin","year":"2020","journal-title":"Am. J. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.31887\/DCNS.2015.17.1\/wgaebel","article-title":"Focus on psychosis","volume":"17","author":"Gaebel","year":"2015","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41588-019-0397-8","article-title":"Genome-wide association study identifies 30 loci associated with bipolar disorder","volume":"51","author":"Stahl","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.schres.2020.06.019","article-title":"A polymorphism in the glutamate metabotropic receptor 7 is associated with cognitive deficits in the early phases of psychosis","volume":"249","author":"Chaumette","year":"2022","journal-title":"Schizophr. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4306\/pi.2014.11.2.186","article-title":"A Disrupted-in-Schizophrenia 1 gene variant is associated with clinical symptomatology in patients with first-episode psychosis","volume":"11","author":"Mata","year":"2014","journal-title":"Psychiatry Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.psychres.2018.05.025","article-title":"Neuregulin 1 (NRG1) gene expression predicts functional outcomes in individuals at clinical high-risk for psychosis","volume":"266","author":"Jagannath","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, H., Xu, J., Lazarovici, P., and Zheng, W. (2017). Dysbindin-1 involvement in the etiology of schizophrenia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102044"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/j.cell.2018.05.046","article-title":"Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes","volume":"173","author":"Ruderfer","year":"2018","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.psychres.2011.12.035","article-title":"Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia","volume":"198","author":"Sun","year":"2012","journal-title":"Psychiatry Res."},{"key":"ref_17","first-page":"325","article-title":"Serotonin transporter gene polymorphisms and auditory hallucinations in psychosis","volume":"50","author":"Rivero","year":"2010","journal-title":"Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.eurpsy.2015.01.008","article-title":"Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia","volume":"30","author":"Cheah","year":"2015","journal-title":"Eur. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jpsychires.2013.11.012","article-title":"Preliminary evidence of an interaction between the FOXP2 gene and childhood emotional abuse predicting likelihood of auditory verbal hallucinations in schizophrenia","volume":"50","author":"Green","year":"2014","journal-title":"J. Psychiatr. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.pnpbp.2010.03.008","article-title":"Possible association of different G72\/G30 SNPs with mood episodes and persecutory delusions in bipolar I Romanian patients","volume":"34","author":"Herms","year":"2010","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/WAD.0000000000000599","article-title":"Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications","volume":"38","author":"Colijn","year":"2024","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s41380-024-02433-8","article-title":"Precision medicine for psychotic disorders: Objective assessment, risk prediction, and pharmacogenomics","volume":"29","author":"Hill","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e145","DOI":"10.1017\/S0033291725001217","article-title":"Characterizing pleiotropy among bipolar disorder, schizophrenia, and major depression: A genome-wide cross-disorder meta-analysis","volume":"55","author":"Friligkou","year":"2025","journal-title":"Psychol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"555.e9","DOI":"10.1016\/j.neurobiolaging.2010.10.003","article-title":"No association of psychosis in Alzheimer disease with neurodegenerative pathway genes","volume":"32","author":"Klei","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1177\/02537176221084867","article-title":"Delusions, Hallucinations, and Cognitive Decline in Middle Age: A Case of Dementia, GIGYF2 Gene Mutation, and 22q11 Duplication","volume":"45","author":"Nadella","year":"2023","journal-title":"Indian J. Psychol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.neulet.2011.10.074","article-title":"Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to antipsychotic treatment in patients with schizophrenia","volume":"506","author":"Crisafulli","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41586-022-04434-5","article-title":"Mapping genomic loci implicates genes and synaptic biology in schizophrenia","volume":"604","author":"Trubetskoy","year":"2022","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Alhassen, W., Chen, S., Vawter, M., Robbins, B.K., Nguyen, H., Myint, T.N., Saito, Y., Schulmann, A., Nauli, S.M., and Civelli, O. (2021). Patterns of cilia gene dysregulations in major psychiatric disorders. Prog. Neuro-Psychopharmacology Biol. Psychiatry, 109.","DOI":"10.1016\/j.pnpbp.2021.110255"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.biopsycho.2007.10.011","article-title":"DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia","volume":"79","author":"Szeszko","year":"2009","journal-title":"Biol. Psychol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/pcn.12290","article-title":"Glia-related genes and their contribution to schizophrenia","volume":"69","author":"Wang","year":"2015","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1001\/archpsyc.65.9.996","article-title":"Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4","volume":"65","author":"Kamiya","year":"2008","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/jnc.15135","article-title":"The neurodevelopmental spectrum of synaptic vesicle cycling disorders","volume":"157","author":"John","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.pnpbp.2011.04.006","article-title":"The impact of glycogen synthase kinase 3 \u03b2 gene on psychotic mania in bipolar disorder patients","volume":"35","author":"Lee","year":"2011","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.biopsych.2022.11.006","article-title":"Associated Genetics and Connectomic Circuitry in Schizophrenia and Bipolar Disorder","volume":"94","author":"Wei","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mikhalitskaya, E.V., Vyalova, N.M., Ermakov, E.A., Levchuk, L.A., Simutkin, G.G., Bokhan, N.A., and Ivanova, S.A. (2023). Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder. Genes, 14.","DOI":"10.3390\/genes14071460"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xue, C.B., Xu, Z.H., Zhu, J., Wu, Y., Zhuang, X.H., Chen, Q.L., Wu, L.C., Hu, J.T., Zhou, H.S., and Xie, W.H. (2019). Exome sequencing identifies TENM4 as a novel candidate gene for schizophrenia in the SCZD2 locus at 11q14-21. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00725"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"RP88117","DOI":"10.7554\/eLife.88117.4","article-title":"Gene\u2013environment pathways to cognitive intelligence and psychotic-like experiences in children","volume":"12","author":"Park","year":"2024","journal-title":"eLife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1192\/bjp.bp.114.159079","article-title":"Association between stressful life events and psychotic experiences in adolescence: Evidence for gene-environment correlations","volume":"208","author":"Shakoor","year":"2016","journal-title":"Br. J. Psychiatry."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8738\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:57Z","timestamp":1760035317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178738"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178738","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}