Nicole R Karcher1, Sarah E Paul2, Emma C Johnson3, Alexander S Hatoum3, David A A Baranger4, Arpana Agrawal3, Wesley K Thompson5, Deanna M Barch6, Ryan Bogdan2. 1. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri. Electronic address: nkarcher@wustl.edu. 2. Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri. 3. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri. 4. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania. 5. Population Neuroscience and Genetics Laboratory, University of California San Diego, San Diego, California. 6. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri.
Abstract
BACKGROUND: Childhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms. METHODS: Adolescent Brain Cognitive Development Study baseline data from children with European ancestry (n = 4650, ages 9-10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models. RESULTS: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔR2s = 0.202%-0.660%; false discovery rate-corrected ps < .006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR2 = 0.120%-0.216%; false discovery rate-corrected ps < .03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated = 3.33%-32.22%). CONCLUSIONS: Total and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.
BACKGROUND: Childhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms. METHODS: Adolescent Brain Cognitive Development Study baseline data from children with European ancestry (n = 4650, ages 9-10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models. RESULTS: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔR2s = 0.202%-0.660%; false discovery rate-corrected ps < .006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR2 = 0.120%-0.216%; false discovery rate-corrected ps < .03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated = 3.33%-32.22%). CONCLUSIONS: Total and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.
Authors: Kathryn M Abel; Susanne Wicks; Ezra S Susser; Christina Dalman; Marianne G Pedersen; Preben Bo Mortensen; Roger T Webb Journal: Arch Gen Psychiatry Date: 2010-09
Authors: Donald J Hagler; SeanN Hatton; M Daniela Cornejo; Carolina Makowski; Damien A Fair; Anthony Steven Dick; Matthew T Sutherland; B J Casey; Deanna M Barch; Michael P Harms; Richard Watts; James M Bjork; Hugh P Garavan; Laura Hilmer; Christopher J Pung; Chelsea S Sicat; Joshua Kuperman; Hauke Bartsch; Feng Xue; Mary M Heitzeg; Angela R Laird; Thanh T Trinh; Raul Gonzalez; Susan F Tapert; Michael C Riedel; Lindsay M Squeglia; Luke W Hyde; Monica D Rosenberg; Eric A Earl; Katia D Howlett; Fiona C Baker; Mary Soules; Jazmin Diaz; Octavio Ruiz de Leon; Wesley K Thompson; Michael C Neale; Megan Herting; Elizabeth R Sowell; Ruben P Alvarez; Samuel W Hawes; Mariana Sanchez; Jerzy Bodurka; Florence J Breslin; Amanda Sheffield Morris; Martin P Paulus; W Kyle Simmons; Jonathan R Polimeni; Andre van der Kouwe; Andrew S Nencka; Kevin M Gray; Carlo Pierpaoli; John A Matochik; Antonio Noronha; Will M Aklin; Kevin Conway; Meyer Glantz; Elizabeth Hoffman; Roger Little; Marsha Lopez; Vani Pariyadath; Susan Rb Weiss; Dana L Wolff-Hughes; Rebecca DelCarmen-Wiggins; Sarah W Feldstein Ewing; Oscar Miranda-Dominguez; Bonnie J Nagel; Anders J Perrone; Darrick T Sturgeon; Aimee Goldstone; Adolf Pfefferbaum; Kilian M Pohl; Devin Prouty; Kristina Uban; Susan Y Bookheimer; Mirella Dapretto; Adriana Galvan; Kara Bagot; Jay Giedd; M Alejandra Infante; Joanna Jacobus; Kevin Patrick; Paul D Shilling; Rahul Desikan; Yi Li; Leo Sugrue; Marie T Banich; Naomi Friedman; John K Hewitt; Christian Hopfer; Joseph Sakai; Jody Tanabe; Linda B Cottler; Sara Jo Nixon; Linda Chang; Christine Cloak; Thomas Ernst; Gloria Reeves; David N Kennedy; Steve Heeringa; Scott Peltier; John Schulenberg; Chandra Sripada; Robert A Zucker; William G Iacono; Monica Luciana; Finnegan J Calabro; Duncan B Clark; David A Lewis; Beatriz Luna; Claudiu Schirda; Tufikameni Brima; John J Foxe; Edward G Freedman; Daniel W Mruzek; Michael J Mason; Rebekah Huber; Erin McGlade; Andrew Prescot; Perry F Renshaw; Deborah A Yurgelun-Todd; Nicholas A Allgaier; Julie A Dumas; Masha Ivanova; Alexandra Potter; Paul Florsheim; Christine Larson; Krista Lisdahl; Michael E Charness; Bernard Fuemmeler; John M Hettema; Hermine H Maes; Joel Steinberg; Andrey P Anokhin; Paul Glaser; Andrew C Heath; Pamela A Madden; Arielle Baskin-Sommers; R Todd Constable; Steven J Grant; Gayathri J Dowling; Sandra A Brown; Terry L Jernigan; Anders M Dale Journal: Neuroimage Date: 2019-08-12 Impact factor: 7.400
Authors: Sophie E Legge; Hannah J Jones; Kimberley M Kendall; Antonio F Pardiñas; Georgina Menzies; Matthew Bracher-Smith; Valentina Escott-Price; Elliott Rees; Katrina A S Davis; Matthew Hotopf; Jeanne E Savage; Danielle Posthuma; Peter Holmans; George Kirov; Michael J Owen; Michael C O'Donovan; Stanley Zammit; James T R Walters Journal: JAMA Psychiatry Date: 2019-12-01 Impact factor: 21.596
Authors: Stanley Zammit; Daphne Kounali; Mary Cannon; Anthony S David; David Gunnell; Jon Heron; Peter B Jones; Shôn Lewis; Sarah Sullivan; Dieter Wolke; Glyn Lewis Journal: Am J Psychiatry Date: 2013-07 Impact factor: 18.112
Authors: Nicole R Karcher; Rachel L Loewy; Mark Savill; Shelli Avenevoli; Rebekah S Huber; Tony J Simon; Ingrid N Leckliter; Kenneth J Sher; Deanna M Barch Journal: Schizophr Bull Open Date: 2020-06-12