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15-09-2021 | Original Article

Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci

Auteurs: Margarita V. Alfimova, Svetlana G. Nikitina, Tatyana V. Lezheiko, Nataliya V. Simashkova, Vera E. Golimbet

Gepubliceerd in: Child Psychiatry & Human Development | Uitgave 1/2023

Abstract

The study explored whether schizophrenia risk alleles of the DRD2 rs2514218 and ZNF804A rs1344706 polymorphisms also influenced the risk and severity of childhood-onset schizophrenia (COS) and differentiated it from autism spectrum disorders (ASD). We compared 75 children with COS to 75 children with ASD, 150 patients with adult-onset schizophrenia and 150 healthy individuals. Frequency of the DRD2 T-allele, assumed to be protective against schizophrenia overall, was higher in COS compared to adult-onset schizophrenia and healthy controls. The risk allele A of ZNF804A was associated with greater severity of negative symptoms in COS. The latter result is consistent with the involvement of ZNF804A in the development of severe forms of schizophrenia. The findings regarding DRD2 suggest that the same genetic variants may play different roles in schizophrenia with childhood and adult onset. This warrants further research, since D2 receptor blockade is a general pharmacodynamic property of antipsychotics.

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Rapoport J, Chavez A, Greenstein D, Addington A, Gogtay N (2009) Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. J Am Acad Child Adolesc Psychiatry 48:10–18CrossRef

Bartlett J (2014) Childhood-onset schizophrenia: what do we really know? Health Psychol Behav Med 2:735–747CrossRef

Kendhari J, Shankar R, Young-Walker L (2016) A review of childhood-onset schizophrenia. Focus (Am Psychiatr Publ) 14:328–332

Driver DI, Thomas S, Gogtay N, Rapoport JL (2020) Childhood-onset schizophrenia and early-onset schizophrenia spectrum disorders: an update. Child Adolesc Psychiatr Clin N Am 29:71–90CrossRef

Owen MJ, O’Donovan MC (2017) Schizophrenia and the neurodevelopmental continuum:evidence from genomics. World Psychiatry 16:227–235CrossRef

Addington AM, Rapoport JL (2009) The genetics of childhood-onset schizophrenia: when madness strikes the prepubescent. Curr Psychiatry Rep 11:156–161CrossRef

Fernandez A, Drozd MM, Thümmler S, Dor E, Capovilla M, Askenazy F et al (2019) Childhood-onset schizophrenia: a systematic overview of its genetic heterogeneity from classical studies to the genomic era. Front Genet 10:1137. https://doi.org/10.3389/fgene.2019.01137CrossRef

Forsyth JK, Asarnow RF (2020) Genetics of childhood-onset schizophrenia 2019 update. Child Adolesc Psychiatr Clin N Am 29:157–170CrossRef

Ahn K, An SS, Shugart YY, Rapoport JL (2016) Common polygenic variation and risk for childhood-onset schizophrenia. Mol Psychiatry 21:94–96CrossRef

10.

Wu Y, Cao H, Baranova A, Huang H, Li S, Cai L et al (2020) Multi-trait analysis for genome-wide association study of five psychiatric disorders. Transl Psychiatry 10:209. https://doi.org/10.1038/s41398-020-00902-6CrossRef

11.

O’Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V et al (2008) Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 40:1053–1055CrossRef

12.

Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427CrossRef

13.

Pardiñas AF, Holmans P, Pocklington AJ, Escott-Price V, Ripke S, Carrera N et al (2018) Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat Genet 50:381–389CrossRef

14.

Brisch R, Saniotis A, Wolf R, Bielau H, Bernstein HG, Steiner J et al (2014) The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry 5:47. https://doi.org/10.3389/fpsyt.2014.00047CrossRef

15.

Wang D, Wang Y, Chen Y, Yu L, Fang X, Liu R et al (2021) Ethnicity-dependent effects of Zinc finger 804A variant on schizophrenia: a systematic review and meta-analysis. Psychiatr Genet 31:21–28CrossRef

16.

Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H et al (2019) Identification of common genetic risk variants for autism spectrum disorder. Nat Genet 51:431–444CrossRef

17.

Squassina A, Meloni A, Chillotti C, Pisanu C (2019) Zinc finger proteins in psychiatric disorders and response to psychotropic medications. Psychiatr Genet 29:132–141CrossRef

18.

Chapman RM, Tinsley CL, Hill MJ, Forrest MP, Tansey KE, Pardiñas AF et al (2019) Convergent evidence that ZNF804A is a regulator of pre-messenger RNA processing and gene expression. Schizophr Bull 45:1267–1278CrossRef

19.

Alfimova MV, Kondratyev NV, Tomyshev AS, Lebedeva IS, Lezheiko TV et al (2019) Effects of a GWAS-supported schizophrenia variant in the DRD2 locus on disease risk, anhedonia, and prefrontal cortical thickness. J Mol Neurosci 68:658–666CrossRef

20.

Lezheiko TV, Romanov DV, Kolesina NY, Golimbet VE (2019) Data on association of the variation (rs1344706) in the ZNF804A gene with schizophrenia and its symptoms in the Russian population. Data Brief 24:103985. https://doi.org/10.1016/j.dib.2019.103985CrossRef

21.

Lezheiko TV, Gabaeva MV, Krikova EV, Golimbet VE (2020) ZNF804A rs1344706 gene polymorphism and clinical heterogeneity of schizophrenia. Res Results Biomed 6(1):51–62. https://doi.org/10.18413/2658-6533-2020-6-1-0-5 (In Russian)CrossRef

22.

Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276CrossRef

23.

Schopler E, Reichler RJ, DeVellis RF, Daly K (1980) Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 10:91–103CrossRef

24.

Toste CC, Duarte RR, Jeffries AR, Selvackadunco S, Troakes C, O’Donovan MC et al (2019) No effect of genome-wide significant schizophrenia risk variation at the DRD2 locus on the allelic expression of DRD2 in postmortem striatum. Mol Neuropsychiatry 5:212–217

25.

GTEx Consortium; Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group; Statistical Methods groups—Analysis Working Group et al (2017) Genetic effects on gene expression across human tissues. Nature 550: 204–213

26.

The 1000 Genomes Project Consortium (2015) A global reference for human genetic variation. Nature 526:68–74CrossRef

27.

Zhang J, Robinson D, Gallego J, John M, Yu J, Addington J et al (2015) Association of a schizophrenia risk variant at the DRD2 locus with antipsychotic treatment response in first-episode psychosis. Schizophr Bull 41:1248–1255CrossRef

28.

Ohira K (2020) Dopamine as a growth differentiation factor in the mammalian brain. Neural Regen Res 15:390–393CrossRef

29.

Bocharova AV, Stepanov VA, Marusin AV, Kharkov VN, Vagaitseva KV, Fedorenko OY et al (2017) Association study of genetic markers of schizophrenia and its cognitive endophenotypes. Russ J Genet 53:139–146CrossRef

30.

Craddock KES, Zhou X, Liu S, Gochman P, Dickinson D, Rapoport JL (2018) Symptom dimensions and subgroups in childhood-onset schizophrenia. Schizophr Res 197:71–77CrossRef

31.

Giannitelli M, Levinson DF, Cohen D, Xavier J (2020) Molecular Genetics of Schizophrenia Collaboration (MGS), Laurent-Levinson C. Developmental and symptom profiles in early-onset psychosis. Schizophr Res 216:470–478CrossRef

32.

Pagsberg AK, Tarp S, Glintborg D, Stenstrøm AD, Fink-Jensen A, Correll CU et al (2014) Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders: protocol for a network meta-analysis of randomised trials. BMJ Open 4(10):e005708. https://doi.org/10.1136/bmjopen-2014-005708CrossRef

Titel: Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci
Auteurs: Margarita V. Alfimova
Svetlana G. Nikitina
Tatyana V. Lezheiko
Nataliya V. Simashkova
Vera E. Golimbet
Publicatiedatum: 15-09-2021
Uitgeverij: Springer US
Gepubliceerd in: Child Psychiatry & Human Development / Uitgave 1/2023
Print ISSN: 0009-398X
Elektronisch ISSN: 1573-3327
DOI: https://doi.org/10.1007/s10578-021-01245-z

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