Table 3.
Summary of Clinical Studies
| Study | Sample; Number of Participants | Childhood Adversity Investigated | Gene-Environment Correlation Between SZ PRS and CA | SZ PRS GWAS | Gene-Environment Interaction Between SZ PRS, CA, and Psychosis |
|---|---|---|---|---|---|
| Guloksuz et al (2019)58 | EU-GEI; 1699 schizophrenia spectrum patients and 1542 controls | Bullying, emotional neglect, physical neglect, emotional abuse, physical abuse, and sexual abuse | Not assessed | PGC2 (2014) | Positive interaction between SZ PRS, case status, and bullying (RERI = 2.76; 95% CI = 0.29, 5.23; P = .028a), emotional abuse (RERI = 5.52; 95% CI = 2.29, 8.75; P < .001a), emotional neglect (RERI = 2.46; 95% CI = 0.98, 3.94; P = .001a), and sexual abuse (RERI = 7.61; 95% CI = 2.05, 13.17; P = .007a). No interaction found for physical abuse (RERI = 1.64; 95% CI = −1.07, 4.34; P = .235) and physical neglect (RERI = 1.51; 95% CI = 0.00, 3.03; P = .051). |
| Trotta et al (2016)48 | GAP; 80 first-episode psychosis cases and 110 unaffected community controls |
Physical/sexual abuse, parental separation, parental death, taken into the care system, and number of family arrangements | Cases: OR = 1.71; 95% CI = −5.37, 8.78; P = .636 | PGC2 (2014) | No significant interaction (b = −0.20; SE = 0.41; P = .632) |
| Zwicker et al (2020)57 | FORBOW; 297 children of parents with psychiatric diagnoses | Childhood maltreatment and peer victimization |
Overall adversity: β = .02; 95% CI = −0.15, 0.18; P = .861 Socioeconomic adversity: β = −.05; 95% CI = −0.20, 0.10; P = .502 Victimization: β = .05; 95% CI = −0.13, 0.23; P = .564 |
PGC2 (2014) | Not assessed |
| Lemvigh et al (2021)59 | Vulnerability Indicators of Psychosis study; 56 proband pairs (schizophrenia spectrum), 49 healthy control pairs, 6 probands without siblings (total n = 216) | General adversity | Not assessed | PGC2 (2014) | No significant interaction: OR = 1.00, 95% CI: 0.48, 2.07, P = .999 |
| Aas et al (2021)47 | EU-GEI; 384 first-episode psychosis cases and 690 controls | General adversity | Case: β = .02; 95% CI = −0.14, 0.22; P = .65 (binary) Case: β = .02; 95% CI = −0.08, 0.11, P = .74 (continuous) |
PGC2 (2014) | Positive interaction between SZ PRS and CA: ICR = 1.28, 95% CI = −1.29, 3.85 |
Note: Abbreviations are explained in the first footnote to table 2. FORBOW, Families Overcoming Risks and Building Opportunities for Well-being; ICR, interaction contrast ratio; RERI, relative excess risk due to interaction. The table describes the clinical studies included in this review and outlines the number of participants with genetic data (by case/control status), the type of childhood adversity investigated, and the outcome.
Effect sizes reported in bold were used in the meta-analysis.
aStudy defined statistical significance.