The association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differences

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dc.authoridAnokhin, Andrey/0000-0001-8158-6346
dc.authorid/0000-0003-2291-6880
dc.authoridFOROUD, TATIANA/0000-0002-5549-2212
dc.authoridEdenberg, Howard/0000-0003-0344-9690
dc.authoridAgrawal, Arpana/0000-0002-0313-793X
dc.authoridJohnson, Emma/0000-0003-0394-777X
dc.authoridPLAWECKI, MARTIN/0000-0003-0708-9514
dc.contributor.authorMeyers, J. L.
dc.contributor.authorChorlian, D. B.
dc.contributor.authorBigdeli, T. B.
dc.contributor.authorJohnson, E. C.
dc.contributor.authorAliev, F.
dc.contributor.authorAgrawal, A.
dc.contributor.authorAlmasy, L.
dc.date.accessioned2024-09-29T16:01:01Z
dc.date.available2024-09-29T16:01:01Z
dc.date.issued2021
dc.departmentKarabük Üniversitesien_US
dc.description.abstractNeurodevelopmental abnormalities in neural connectivity have been long implicated in the etiology of schizophrenia (SCZ); however, it remains unclear whether these neural connectivity patterns are associated with genetic risk for SCZ in unaffected individuals (i.e., an absence of clinical features of SCZ or a family history of SCZ). We examine whether polygenic risk scores (PRS) for SCZ are associated with functional neural connectivity in adolescents and young adults without SCZ, whether this association is moderated by sex and age, and if similar associations are observed for genetically related neuropsychiatric PRS. One-thousand four-hundred twenty-six offspring from 913 families, unaffected with SCZ, were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort (median age at first interview = 15.6 (12-26), 51.6% female, 98.1% European American, 41% with a family history of alcohol dependence). Participants were followed longitudinally with resting-state EEG connectivity (i.e., coherence) assessed every two years. Higher SCZ PRS were associated with elevated theta (3-7 Hz) and alpha (7-12 Hz) EEG coherence. Associations differed by sex and age; the most robust associations were observed between PRS and parietal-occipital, central-parietal, and frontal-parietal alpha coherence among males between ages 15-19 (B: 0.15-0.21, p < 10(-4)). Significant associations among EEG coherence and Bipolar and Depression PRS were observed, but differed from SCZ PRS in terms of sex, age, and topography. Findings reveal that polygenic risk for SCZ is robustly associated with increased functional neural connectivity among young adults without a SCZ diagnosis. Striking differences were observed between men and women throughout development, mapping onto key periods of risk for the onset of psychotic illness and underlining the critical importance of examining sex differences in associations with neuropsychiatric PRS across development.en_US
dc.description.sponsorshipNIH from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA008401]; National Institute on Drug Abuse (NIDA); 2019 BBRF Young Investigator Grant; National Institutes of Health [U10AA008401]en_US
dc.description.sponsorshipCOGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, D. Dick, includes 11 different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, J. Nurnberger Jr., M. Plawecki, Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St. Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks, R. Hart); The Children's Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick, J. Salvatore); Icahn School of Medicine at Mount Sinai (A. Goate, M. Kapoor, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); L. Wetherill, X. Xuei, D. Lai, S. O'Connor, M. Plawecki, S. Lourens (Indiana University); L. Acion (University of Iowa); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, S. Kinreich, G. Pandey (SUNY Downstate); M. Chao (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); F. Aliev, P. Barr (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). This research is supported by a 2019 BBRF Young Investigator Grant (PI: JL. Meyers) and funding from the National Institutes of Health (U10AA008401).en_US
dc.identifier.doi10.1038/s41398-020-01185-7
dc.identifier.issn2158-3188
dc.identifier.issue1en_US
dc.identifier.pmid33446638en_US
dc.identifier.scopus2-s2.0-85099475621en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1038/s41398-020-01185-7
dc.identifier.urihttps://hdl.handle.net/20.500.14619/5492
dc.identifier.volume11en_US
dc.identifier.wosWOS:000610538300007en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringernatureen_US
dc.relation.ispartofTranslational Psychiatryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectGenome-Wide Associationen_US
dc.subjectEeg Coherenceen_US
dc.subject1st-Episode Schizophreniaen_US
dc.subjectFunctional Connectivityen_US
dc.subjectIdentifies 30en_US
dc.subjectOscillationsen_US
dc.subjectLinkageen_US
dc.subjectLocien_US
dc.subjectSynchronizationen_US
dc.subjectAbnormalitiesen_US
dc.titleThe association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differencesen_US
dc.typeArticleen_US

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