Content area
Background
Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability.
Methods
Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals.
Results
SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences.
Conclusions
SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.
Details
Accuracy;
Cognition;
Psychopathology;
Schizophrenia;
Mental disorders;
Risk assessment;
Families & family life;
Affective disorders;
Standard scores;
Environmental aspects;
Externalizing problems;
Child Behavior Checklist;
Aggressive behavior;
Child development;
Psychosis;
Mental depression;
Associations;
Cognitive development;
Internalization;
Psychotic symptoms;
Cognitive-behavioral factors;
Intellectual development;
Emotional behavior;
Generalizability;
Children & youth;
Behavior;
Emotional disorders;
Childhood;
Youth;
Brain;
Behavior problems;
Children;
Liability;
Genetics;
Adolescent development;
Disorders;
Symptoms
; Zhu, Jinhan 1 ; Boltz, Toni A. 2
; Conomos, Matthew P. 3
; Hughes, Dylan E. 4
; Fohner, Alison E. 5
; Foster, Katherine T. 6
; Bigdeli, Tim B. 7
; Forsyth, Jennifer K. 5 1 Department of Psychology, https://ror.org/00cvxb145 University of Washington, Seattle, WA, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
3 Department of Biostatistics, https://ror.org/00cvxb145 University of Washington, Seattle, WA, USA
4 Department of Psychology, University of California, Los Angeles, CA, USA
5 Institute for Public Health Genetics, https://ror.org/00cvxb145 University of Washington, WA, USA
6 Department of Global Health, https://ror.org/00cvxb145 University of Washington, WA, USA
7 Department of Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, USA