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Evocative gene‐environment correlation between genetic risk for schizophrenia and bullying victimization

2019; Wiley; Volume: 18; Issue: 3 Linguagem: Inglês

10.1002/wps.20685

2051-5545

Giulio Pergola, Marco Papalino, Barbara Gelao, Leonardo Sportelli, Wilma Vollerbergh, Ignazio Grattagliano, Alessandro Bertolino,

Child and Adolescent Psychosocial and Emotional Development

World PsychiatryVolume 18, Issue 3 p. 366-367 Letter to the EditorFree Access Evocative gene-environment correlation between genetic risk for schizophrenia and bullying victimization Giulio Pergola, Giulio Pergola Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USASearch for more papers by this authorMarco Papalino, Marco Papalino Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorBarbara Gelao, Barbara Gelao Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorLeonardo Sportelli, Leonardo Sportelli Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorWilma Vollerbergh, Wilma Vollerbergh Department of Interdisciplinary Social Science, Utrecht University, Utrecht, The NetherlandsSearch for more papers by this authorIgnazio Grattagliano, Ignazio Grattagliano Department of Educational Sciences, Psychology and Communication, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorAlessandro Bertolino, Alessandro Bertolino Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy Psychiatry Unit, Bari University Hospital, Bari, ItalySearch for more papers by this author Giulio Pergola, Giulio Pergola Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USASearch for more papers by this authorMarco Papalino, Marco Papalino Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorBarbara Gelao, Barbara Gelao Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorLeonardo Sportelli, Leonardo Sportelli Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorWilma Vollerbergh, Wilma Vollerbergh Department of Interdisciplinary Social Science, Utrecht University, Utrecht, The NetherlandsSearch for more papers by this authorIgnazio Grattagliano, Ignazio Grattagliano Department of Educational Sciences, Psychology and Communication, University of Bari Aldo Moro, Bari, ItalySearch for more papers by this authorAlessandro Bertolino, Alessandro Bertolino Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy Psychiatry Unit, Bari University Hospital, Bari, ItalySearch for more papers by this author First published: 09 September 2019 https://doi.org/10.1002/wps.20685Citations: 4 The authors thank A.J. Oldehinkel and the TRAILS Consortium for sharing the data, G. Arciero and T. Quarto for insightful discussions, and P. Di Carlo for methodological advice. The study was funded by the European Union's Horizon 2020 under the Marie Sklodowska-Curie actions programme FLOURISH (no. 798181). AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Bullying victimization (BV) is a risk factor for the development of psychotic experiences and psychotic disorders1, 2. We used data from TRAILS (TRacking Adolescents' Individual Lives Survey), a longitudinal cohort study of Dutch pre-adolescents3, to study the relationship between polygenic risk score for schizophrenia (SCZ-PRS) and BV, and the possible role of BV in mediating the effect of genetic risk for schizophrenia on the development of psychotic symptoms later in life. Three assessment waves of TRAILS – T1 (10-12.5 years old), T2 (12.4-14.6 years old) and T3 (14.8-18.3 years old) – were considered. We assessed IQ using the Wechsler Intelligence Scale for Children (WISC), administered at T1; BV through peer nomination scores at T1 and T2; social competence at T1 using the Revised Class Play (RCP); teacher-reported relational aggression by Likert scales at T2; and lifetime psychotic experiences using the Community Assessment of Psychic Experiences Scale at T3. We imputed TRAILS genotypic data using Sanger Imputation Service (1000 Genomes Project Phase 3 reference GRCh37/hg19). We excluded siblings and pupils on special education, checked genotype quality, derived genomic components to control for ancestry, and computed individual polygenic risk scores (PRS) for schizophrenia, attention-deficit/hyperactivity disorder, autism, bipolar disorder, major depression, and obsessive-compulsive disorder, using standard procedures4. We focused on PRS-6 (including variants with association p-value 0.05). ANOVA at T2 returned a significant PRS effect on BV (N=625, F2,611=3.4, p=0.033, partial η2=0.011; observed power = 64%). High PRS individuals had greater peer nomination scores compared to medium PRS subjects (N=417, p=0.017) as well as to a merged sample of low/medium risk individuals (N=625, F1,613=6.3, p=0.012, partial η2=0.01, observed power = 71%). SCZ-PRS was directly associated with BV at T2, without significant mediation by social competence at T1 (N=558, partially standardized effect = 0.011). T2 mediation analysis revealed a significant indirect effect of genetic risk on psychotic experiences at T3 (N=610, partially standardized effect = 0.031). Victims suffered more frequent psychotic experiences at T3 (N=610, p=0.018). These results suggest that BV partially mediated the effect of SCZ-PRS on the frequency of psychotic symptoms developed at T3. When BV was assessed based on both peer and teacher report at T2, the effect was even larger, despite the reduced sample size (N=390, p=0.002). Only genetic risk for schizophrenia, and not for other disorders, was associated with BV. Only BV peer nomination, not other peer nomination measures, was associated with later psychotic symptoms. In summary, we found that 13-14-year-old adolescents with greater SCZ-PRS experienced more severe bullying than their peers with lower SCZ-PRS, and that BV partially mediated the effect of genetic risk on the development of later psychotic symptoms. A possible mechanism through which this mediation may occur is evocative gene-environment correlation, i.e., the genetic risk carrier evoking particular reactions of other individuals, such as bullying. The effect is small (1% of the variance), but it is in line with other reported effects, e.g., SCZ-PRS explains at most 1.2% of the variance in symptoms across patients with schizophrenia. Our sample sizes are small for a behavioral genetics study, a limitation we attempted to address by cumulating risk variants into PRS tertiles. Peer nomination is just one way to assess BV and results may differ based on other reporters6, 7. However, findings persisted when assessing BV based on peer/teacher reports. Importantly, we did not use self-reports, which may be influenced by paranoia. The prospective data collection reduced the risk of retrospective memory bias. We studied risk for schizophrenia, but used psychotic episodes as a clinical proxy. Schizophrenia risk may overlap only partially with risk for psychosis, but risk variants for psychosis are not known. To the extent that genetic risk translation into clinical symptoms is mediated by environmental risk8, our findings call for efforts to antagonize BV of vulnerable individuals to support mental health prevention6, 9. References 1 Singham T, Viding E, Schoeler T et al. JAMA Psychiatry 2017; 74: 1112- 9. CrossrefPubMedWeb of Science®Google Scholar 2 Radua J, Ramella-Cravaro V, Ioannidis JPA et al. World Psychiatry 2018; 17: 49- 66. Wiley Online LibraryPubMedWeb of Science®Google Scholar 3 Oldehinkel AJ, Rosmalen JGM, Buitelaar JK et al. Int J Epidemiol 2015; 44: 76- 76n. CrossrefPubMedWeb of Science®Google Scholar 4 Chen Q, Ursini G, Romer AL et al. Brain 2018; 141: 1218- 28. CrossrefPubMedWeb of Science®Google Scholar 5 Schizophrenia Working Group of the Psychiatric Genomics Consortium. Nature 2014; 511: 421- 7. CrossrefCASPubMedWeb of Science®Google Scholar 6 Bowes L, Maughan B, Ball H et al. Dev Psychopathol 2013; 25: 333- 46. CrossrefPubMedWeb of Science®Google Scholar 7 Shakoor S, McGuire P, Cardno AG et al. Schizophr Bull 2015; 41: 754- 63. CrossrefPubMedWeb of Science®Google Scholar 8 Uher R, Zwicker A. World Psychiatry 2017; 16: 121- 9. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 9 Arsenault L. World Psychiatry 2017; 16: 27- 8. Wiley Online LibraryPubMedWeb of Science®Google Scholar Citing Literature Volume18, Issue3October 2019Pages 366-367 ReferencesRelatedInformation