Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.
Childhood trauma
first-episode psychosis
interaction contrast ratio
polygenic risk
schizophrenia
synergistic effects
Journal
Psychological medicine
ISSN: 1469-8978
Titre abrégé: Psychol Med
Pays: England
ID NLM: 1254142
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
medline:
15
6
2023
pubmed:
13
6
2023
entrez:
13
6
2023
Statut:
ppublish
Résumé
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR) There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Sections du résumé
BACKGROUND
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
METHODS
We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)
RESULTS
There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88).
CONCLUSIONS
Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Identifiants
pubmed: 37310339
doi: 10.1017/S0033291721003664
pii: S0033291721003664
pmc: PMC10106300
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1970-1978Subventions
Organisme : Medical Research Council
ID : MR/S003444/1
Pays : United Kingdom
Références
JAMA Psychiatry. 2019 Jan 1;76(1):79-86
pubmed: 30477014
Arch Gen Psychiatry. 1991 Aug;48(8):764-70
pubmed: 1883262
Med Hypotheses. 2014 Sep;83(3):276-81
pubmed: 24957505
PLoS Genet. 2013 Mar;9(3):e1003348
pubmed: 23555274
JAMA Psychiatry. 2019 Jun 1;76(6):584-593
pubmed: 30892562
Schizophr Res. 2019 Nov;213:65-71
pubmed: 30660575
Schizophr Res. 2019 Mar;205:51-57
pubmed: 29653893
Am J Psychiatry. 1994 Aug;151(8):1132-6
pubmed: 8037246
Lancet Psychiatry. 2019 May;6(5):427-436
pubmed: 30902669
Soc Psychiatry Psychiatr Epidemiol. 2002 Jul;37(7):329-35
pubmed: 12111025
Schizophr Bull. 2012 Jun;38(4):661-71
pubmed: 22461484
Schizophr Res. 2016 Oct;176(2-3):171-176
pubmed: 27344984
Acta Psychiatr Scand. 2014 Oct;130(4):311-7
pubmed: 24961959
Soc Psychiatry Psychiatr Epidemiol. 2020 May;55(5):645-657
pubmed: 31974809
Front Psychol. 2017 Aug 24;8:1276
pubmed: 28883800
Schizophr Res. 2013 Nov;150(2-3):356-65
pubmed: 24094883
Int J Epidemiol. 2007 Oct;36(5):1111-8
pubmed: 17726040
Biol Psychiatry. 2017 Mar 15;81(6):470-477
pubmed: 27765268
Epidemiology. 1992 Sep;3(5):452-6
pubmed: 1391139
Psychol Med. 2019 Jun;49(8):1378-1391
pubmed: 30282569
World Psychiatry. 2019 Jun;18(2):173-182
pubmed: 31059627
Schizophr Res. 2019 Mar;205:58-62
pubmed: 29793818
J Psychiatr Res. 2014 Dec;59:14-21
pubmed: 25246365
J Psychiatr Res. 2018 Jan;96:57-64
pubmed: 28965006
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Biol Psychiatry. 2002 Oct 15;52(8):843; author reply 843-5
pubmed: 12372656
Schizophr Res. 2005 Nov 1;79(1):59-68
pubmed: 16005191
Br J Psychiatry. 2014 Aug;205(2):113-9
pubmed: 24925986
Am J Psychiatry. 2019 Oct 1;176(10):846-855
pubmed: 31416338
J Child Psychol Psychiatry. 2016 Oct;57(10):1103-12
pubmed: 27647050
JAMA Psychiatry. 2018 Jan 1;75(1):36-46
pubmed: 29214289
Int J Bipolar Disord. 2016 Dec;4(1):2
pubmed: 26763504
Schizophr Bull. 2008 Jan;34(1):193-9
pubmed: 17586579
Psychol Med. 2016 Mar;46(4):759-70
pubmed: 26526099
Bipolar Disord. 2020 Mar;22(2):174-181
pubmed: 31628696
Schizophr Bull. 2018 Oct 17;44(6):1195-1203
pubmed: 29762765
Lancet. 2014 May 10;383(9929):1677-1687
pubmed: 24315522
Biol Psychiatry. 2018 Mar 15;83(6):492-498
pubmed: 28987712
Genome Med. 2017 Nov 13;9(1):96
pubmed: 29132412
Int J Epidemiol. 2012 Apr;41(2):514-20
pubmed: 22253321
Nature. 2009 Aug 6;460(7256):748-52
pubmed: 19571811
Eur Arch Psychiatry Clin Neurosci. 2017 Feb;267(1):1-2
pubmed: 28070643
Biol Psychiatry. 2018 Jul 15;84(2):138-147
pubmed: 29129318
Psychol Med. 2007 Oct;37(10):1377-91
pubmed: 17335638
Can J Psychiatry. 2013 Jan;58(1):44-51
pubmed: 23327756
Neurosci Biobehav Rev. 2017 Feb;73:191-218
pubmed: 27993603
Child Abuse Negl. 2001 Sep;25(9):1177-200
pubmed: 11700691
PLoS One. 2016 Sep 20;11(9):e0163319
pubmed: 27648571
Nat Genet. 2019 Jul;51(7):1193
pubmed: 31160808
Psychol Rev. 1997 Oct;104(4):667-85
pubmed: 9337628
Brain Res. 1990 Jun 25;521(1-2):311-5
pubmed: 2119850