» Articles » PMID: 33635441

Schizophrenia Polygenic Risk is Associated with Child Mental Health Problems Through Early Childhood Adversity: Evidence for a Gene-environment Correlation

Overview
Specialties Pediatrics
Psychiatry
Date 2021 Feb 26
PMID 33635441
Citations 6
Authors
Affiliations
Soon will be listed here.
Abstract

Previous studies have shown that schizophrenia polygenic risk predicts a multitude of mental health problems in the general population. Yet it is unclear by which mechanisms these associations arise. Here, we explored a possible gene-environment correlation in the association of schizophrenia polygenic risk with mental health problems via childhood adversity. This study was embedded in the population-based Generation R Study, including N = 1901 participants with genotyping for schizophrenia polygenic risk, maternal reporting of childhood adversity, and Child Behaviour Checklist measurement of mental health problems. Independent replication was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3641). Associations were analysed with Poisson regression and statistical mediation analysis. Higher burden of schizophrenia polygenic risk was associated with greater exposure to childhood adversity (P-value threshold < 0.5: Generation R Study, OR = 1.08, 95%CI 1.02-1.15, P = 0.01; ALSPAC, OR = 1.02, 95%CI 1.01-1.03, P < 0.01). Childhood adversities partly explained the relationship of schizophrenia polygenic risk with emotional, attention, and thought problems (proportion explained, range 5-23%). Direct effects of schizophrenia polygenic risk and adversity on mental health outcomes were also observed. In summary, genetic liability to schizophrenia increased the risk for mental health problems in the general paediatric population through childhood adversity. Although this finding could result from a mediated causal relationship between genotype and mental health, we argue that these observations most likely reflect a gene-environment correlation, i.e. adversities are a marker for the genetic risk that parents transmit to children. These and similar recent findings raise important conceptual questions about preventative interventions aimed at reducing childhood adversities.

Citing Articles

Clinical characteristics of psychotic disorders in patients with childhood trauma.

Lovric S, Klaric M, Lovric I, Camber R, Kresic Coric M, Kvesic J Medicine (Baltimore). 2023; 102(51):e36733.

PMID: 38134067 PMC: 10735130. DOI: 10.1097/MD.0000000000036733.


Childhood trauma and suicide risk in hospitalized patients with schizophrenia: the sequential mediating roles of pandemic related post-traumatic stress symptoms, sleep quality, and psychological distress.

Xie M, Zou X, Xie Y, Hu L, Tang Y, Cai J Front Psychiatry. 2023; 14:1221529.

PMID: 37810605 PMC: 10551446. DOI: 10.3389/fpsyt.2023.1221529.


A Prospective Cohort Study on the Intergenerational Transmission of Childhood Adversity and Subsequent Risk of Psychotic Experiences in Adolescence.

Bolhuis K, Steenkamp L, Tiemeier H, Blanken L, Pingault J, Cecil C Schizophr Bull. 2022; 49(3):799-808.

PMID: 36548471 PMC: 10154714. DOI: 10.1093/schbul/sbac195.


Schizophrenia Polygenic Risk and Experiences of Childhood Adversity: A Systematic Review and Meta-analysis.

Woolway G, Smart S, Lynham A, Lloyd J, Owen M, Jones I Schizophr Bull. 2022; 48(5):967-980.

PMID: 35674151 PMC: 9434424. DOI: 10.1093/schbul/sbac049.


Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults.

Marchi M, Elkrief L, Alkema A, van Gastel W, Schubart C, van Eijk K Transl Psychiatry. 2022; 12(1):219.

PMID: 35650188 PMC: 9160238. DOI: 10.1038/s41398-022-01975-1.


References
1.
Sallis H, Croft J, Havdahl A, Jones H, Dunn E, Davey Smith G . Genetic liability to schizophrenia is associated with exposure to traumatic events in childhood. Psychol Med. 2020; 51(11):1814-1821. PMC: 8381289. DOI: 10.1017/S0033291720000537. View

2.
Cheesman R, Hunjan A, Coleman J, Ahmadzadeh Y, Plomin R, McAdams T . Comparison of Adopted and Nonadopted Individuals Reveals Gene-Environment Interplay for Education in the UK Biobank. Psychol Sci. 2020; 31(5):582-591. PMC: 7238511. DOI: 10.1177/0956797620904450. View

3.
Euesden J, Lewis C, OReilly P . PRSice: Polygenic Risk Score software. Bioinformatics. 2015; 31(9):1466-8. PMC: 4410663. DOI: 10.1093/bioinformatics/btu848. View

4.
Zheutlin A, Dennis J, Linner R, Moscati A, Restrepo N, Straub P . Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems. Am J Psychiatry. 2019; 176(10):846-855. PMC: 6961974. DOI: 10.1176/appi.ajp.2019.18091085. View

5.
Yang J, Lee S, Goddard M, Visscher P . GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2010; 88(1):76-82. PMC: 3014363. DOI: 10.1016/j.ajhg.2010.11.011. View