Cumulative Risk Effect Research Articles

History of Multiple Allergies and Gradual Onset Running-Related Injuries in Distance Runners: SAFER XXXV.

To determine if any gradual onset running-related injury (GORRI) was associated with any allergies, multiple allergies (allergies to animals, plants, medication), and allergy medication use. Cross-sectional descriptive study. Two Oceans Marathons (56 km, 21.1 km), South Africa. A total of 76 654 race entrants (2012-2015). The prevalence (%) and prevalence ratios (PR; 95% confidence intervals) for history of (1) any allergies, (2) multiple allergies to broad categories of allergens (animal material, plant material, allergies to medication, and other allergies), and (3) allergy medication use. Using a compulsory online screening questionnaire, the outcome was a history of any GORRIs, and subcategories of GORRIs (muscle, tendon) in the past 12 months and history of GORRIs (and subtypes of GORRIs) were reported. In 68 258 records with injury and allergy data, the following were significantly associated with reporting any GORRIs: a history of any allergy (PR = 2.2; P < 0.0001), a history of allergies to broad categories of allergens (animal, plant, medication allergy, other) (P < 0.0001), and the use of allergy medication (P < 0.0001). A history of any allergies (PR = 2.4; P < 0.0001), all broad categories of allergies, and allergy medication use were significantly associated with muscle (P < 0.0001) and tendon injuries (P < 0.0001). The risk of reporting a GORRI increased as the number of reported categories of allergies increased (P < 0.0001). A novel finding was the cumulative risk effect with a history of multiple allergies. Further studies should aim to determine the underlying mechanism relating allergies and GORRIs.

Episodic foresight, episodic memory, and executive functions in children engaged with Child Protective Services: The role of cumulative risk

Previous studies have determined that exposure to risk and adversities may impair children’s cognitive abilities. In particular, children engaged with Child Protective Services (CPS) seem to be at greater risk for enhanced detrimental effects resulting from the cumulative risk factors to which they are exposed. However, little is known about children’s future thinking when they face adverse circumstances, and it is not clear how the associations among episodic foresight abilities, episodic memory, and executive functions work with children under such circumstances. The current study describes the episodic foresight abilities of CPS-involved school-aged children, its association with other cognitive abilities, and how this association is affected by the exposure to cumulative risk and adversity factors. Episodic foresight, episodic memory, executive functions, and a composite of cumulative risk factors were analyzed in a sample of 95 school-aged children engaged with CPS in Portugal. Results suggest the detrimental effect of cumulative risk on the episodic foresight abilities of CPS-involved children. Episodic memory and cognitive flexibility were significant predictors of episodic foresight abilities, and cumulative risk exposure moderated the relation between episodic memory and episodic foresight. The current study provides a better understanding of the influences of multiple adversities on CPS-involved children’s episodic foresight abilities and related cognitive outcomes.

Parental risk factors and children entering out-of-home care: The effects of cumulative risk and parent’s sex

BackgroundParental difficulties, including mental ill health, substance misuse, domestic violence and learning disability have been associated with children entering out-of-home care. There is also evidence that these issues may co-occur within families. Understanding how the co-occurrence of these difficulties is associated with care entry is complex because they may co-occur in the same or different household members and have different impacts on the likelihood of care entry when they occur in mothers, fathers or in single parent households. MethodAdministrative data from local authority children’s services in Wales were linked with demographic data to identify households in which children lived prior to entering care. Linkage to birth data identified biological mothers. Linkage with primary care, emergency department, hospital admissions and substance misuse services data enabled indicators of substance misuse, mental health, assaults in the home, learning disability and neurodivergence in the adults in those households to be identified. A series of multilevel binary logistic regression models were used to explore the odds of a household having one or more children entering care if risk factors were present. These considered the effects of individual risks, and cumulative risk both in individual adults in the household, and across the whole household. The effects of the number of adults, having adults with no risks and the differential impacts of risks in biological mothers, other women or men were also explored. Additional models explored these factors in single adult households. ResultsCumulative risks increased the likelihood of care entry, however this effect disappeared when individual risks were controlled for. The presence of an individual with no risks in the household acted as a protective factor. Overall, the impact of the risks on the odds of care entry was substantially greater if the risks were present in the biological mother than if they occurred in other adults (men or women) in the household. In single adult households risk factors had a much greater impact when they occurred in households headed by women as opposed to men. ConclusionSubstantial differences in the effects of risk factors in female and male adults are apparent and further research is needed to understand why this is occurring to ensure that parents are treated equally in terms of support and statutory intervention regardless of their sex.11Throughout this paper we refer to the “sex” of the parents /adults in households, as opposed to their “gender.” This is because in the analysis we carried out the sex of these individuals was determined by their GP records. We have chosen to use the term “sex,” rather than “gender,” as we believe this data is more likely to reflect their biological sex, rather the gender that the individuals identify as.

Cumulative Ecological Risk and Chinese Adolescent Internet Addiction During the COVID-19 Pandemic: The Mediating Role of Self-Control and the Moderating Role of Negotiable Fate

ABSTRACT On January 30, 2020, the World Health Organization (WHO) announced that the COVID-19 epidemic was declared an international public health emergency. Since that time, the epidemic has had a significant impact on the psychological and behavioral adaptation of individuals worldwide. To explore the mediating role of self-control and the moderating role of negotiation fate in the relationship between cumulative ecological risk and adolescent internet addiction during the COVID-19 pandemic, cumulative ecological risk questionnaires were administered to 637 junior high school students, including the Self-Control scale, Negotiable Fate scale, and Internet Addiction scale. The results showed that (1) cumulative ecological risk was significantly positively correlated with internet addiction; (2) self-control mediated the relationship between cumulative work risk and internet addiction; and (3) both the direct effect of cumulative ecological risk on internet addiction and the first half of the indirect effect of affect self-control were moderated by negotiable fate. Our results may help us better understand the relationship between cumulative ecological risk and internet addiction during the COVID-19 pandemic.

The hidden curves of risk: a nonlinear model of cumulative risk and school bullying victimization among adolescents with autism spectrum disorder

BackgroundSchool bullying victimization (SBV) occurs more frequently in students with autism spectrum disorder (ASD) in general education than in special classes, and there is a cumulative risk effect on SBV exposure among young people with ASD reported by their parents and teachers. However, SBV is a personal experience, the predictive patterns of cumulative risk on SBV reported by themselves and its psychological mechanism remain unclear. This study aims to explore the relationship between cumulative risk and SBV based on self-report, and to test whether internalizing problems mediates this relationship among adolescents with ASD placed in regular classes.MethodsThis study used data from the Taiwan Special Needs Education Longitudinal Study (SNELS) in 2011. The analysis included 508 adolescents with ASD who were in regular classes across Taiwan. The primary variables under study were the quality of friendship interactions, teacher-student relationship, school connection, perceived stigma, the impact caused by the disabilities, internalizing problem, and whether the participants had experienced SBV over the past semester, while control variables were adaptability and social-emotional skills. Established risk factors were summed to form a cumulative risk score.ResultsThe cumulative risk was positively associated with SBV. The relationship was characterized by the nonlinear pattern of the quadratic function (negative acceleration model) between cumulative risk and SBV. Internalizing problem played a partial mediating role in the effect of cumulative risk on SBV.ConclusionsIntervention measures to reduce SBV should include the strategies to reduce the number of risks to which adolescents with ASD in regular classes are exposed, comprehensive prevention targeting each risk factor is needed specially when the number of risks is one or two, and more attention needs to be given to their internalizing problem in various ways.

The Effect of Cumulative Ecological Risk on College Students’ Study Engagement: A Mediation of Self-affirmation

The Effect of Cumulative Ecological Risk on College Students’ Study Engagement: A Mediation of Self-affirmation

Cumulative ecological risk and nonsuicidal self-injury in adolescents: The mediation of depression and the moderation of impulsiveness.

This study is based on the biosocial model of nonsuicidal self-injury (NSSI), to explore the effects of cumulative ecological risk on adolescents' NSSI, the mediating effect of depression between cumulative ecological risk and adolescents' NSSI, and the moderating role of impulsiveness in this mediating pathway. A total of 16 508 adolescents, with 7903 males (47.9%), participated in the study and completed the Cumulative Ecological Risk Questionnaire, the Short Form of the Center for Epidemiological Studies Depression Scale, the Impulsiveness assessment, and the Nonsuicidal Self-Injury Scale. (1) There was a significant positive correlation between cumulative ecological risk, depression, impulsiveness, and NSSI; (2) cumulative ecological risk significantly predicted adolescents' NSSI; (3) depression had a mediating effect between cumulative ecological risk and adolescents' NSSI; and (4) impulsiveness moderated both the effects of cumulative ecological risk on adolescents' depression and NSSI and the effects of depression on NSSI in adolescents. Impulsiveness and depression are risk factors for adolescent NSSI and play a crucial role between cumulative ecological risk and NSSI in adolescents.

Gender differences in the longitudinal association between cumulative ecological risk and smartphone dependence among early adolescents: A parallel mediation model

Early adolescent smartphone dependence has emerged as a significant social and public health issue. Previous research showed that multiple ecological risks including family, school, and peer risk factors played important roles in early adolescent smartphone dependence. However, these studies have examined risk factors individually rather than examining the cumulative risk effect. Based on the Ecological Systems Theory and Risk-Protective Factor Theory, the present study focused on the longitudinal association between cumulative ecological risk and early adolescent smartphone dependence. We tested two mediating mechanisms of this association, namely social anxiety and self-compassion, and examined possible gender differences in these mediation processes. The study adopted a three-wave longitudinal design spanning one year, with a six-month interval between each wave. 357 secondary school students (Mage = 12.58 years, SD = 0.61, 52.1% girls) from two middle schools in China participated in this study. As expected, cumulative ecological risk positively predicted smartphone dependence one year later, and social anxiety and self-compassion were parallel mediators of this longitudinal association. Meanwhile, there were gender differences in the mediation model. The results provide a theoretical and empirical basis for the development of prevention and intervention strategies and public health policies to reduce the likelihood of early adolescents' smartphone dependence.

Young Children's Development and Behavior: Associations with Timing of Household Food Insecurity in a Racially and Ethnically Diverse Early Head Start Sample.

The objective of this study was to assess the impact of household food insecurity (HFI) over time on behavioral and developmental health in early childhood while considering the impact of timing/persistence of HFI and potential differences among racially or ethnically minoritized children. Families from the Early Head Start Family and Child Experiences Study (N = 760) were followed longitudinally until age 3 years. Caregiver interview data were collected on HFI, problem behaviors (PBs), delays in development (DD), and sociodemographic information. Analysis of Covariances examined differences between persistent vs transient HFI. Multiple regressions examined the impact of HFI on PB and DD and whether this relation was stronger in racially or ethnically minoritized children. The timing of HFI differentially affected PB, such that those with persistent HFI demonstrated greater PB than those with only early or only late HFI. A different pattern was identified for DD, in which those with late HFI had more DD than those with persistent HFI. Over and above other sociodemographics, including maternal risk factors and an income-to-needs ratio, HFI was associated with greater PB for children of all races and ethnicities. HFI was associated with more DD in non-Latino/a/e/x White families compared with non-Latino/a/e/x Black and Latino/a/e/x families. Meaningful differences were found in how the persistence/timing of HFI is differentially associated with PB and DD. In addition, while controlling for socioeconomic risk, a cumulative risk effect was not observed in how HFI affected racially or ethnically minoritized children.

Cumulative Risk and Externalizing Behaviors during Infancy in a Predominantly Latine Sample

Externalizing behavior problems are among the top mental health concerns in early childhood, and many parenting interventions have been developed to address this issue. To better understand predictors of parenting intervention outcomes in high-risk families, this secondary data analysis evaluated the moderating effect of cumulative risk on child externalizing behaviors, parenting skills, and intervention dropout after completion of a home-based adaptation of the child-directed interaction phase of parent-child interaction therapy (PCIT) called the Infant Behavior Program (IBP). The participants included 58 toddlers (53% male; average age of 13.5 months; and 95% Hispanic or Latine) who were part of a larger randomized control trial in which families were randomly assigned to receive the IBP or treatment as usual (TAU). Cumulative risk was found to moderate the effect of the intervention group on child externalizing behaviors such that the participants in the intervention group with higher cumulative risk scores had greater reductions in externalizing behaviors. A potential explanation for these unexpected findings may be that the obstacles to treatment that were previously imposed by comorbid risk factors (i.e., lack of transportation, time commitment, and language barriers) were adequately addressed such that the families who most needed the intervention were able to remain fully engaged.

Cumulative Ecological Risk and Academic Burnout in Chinese College Students: A Moderated Mediation Model.

This study explored the relationship between cumulative ecological risk exposure and academic burnout among Chinese college students and the mediating and moderating effects of neuroticism and gender, respectively. A total of 580 college students were selected as participants. They completed a battery of questionnaires that measured cumulative ecological risk, neuroticism, and academic burnout. The results showed that: (1) cumulative ecological risk was positively related to neuroticism and academic burnout; (2) cumulative ecological risk positively predicted academic burnout; (3) neuroticism partly mediated the relationship between cumulative ecological risk and academic burnout; and (4) gender moderated the effect of cumulative ecological risk and academic burnout. A high level of cumulative ecological risk had a greater impact on neuroticism among women, compared to men. These findings advance our current knowledge of the specific effects of cumulative ecological risk on academic burnout and the underlying internal mechanisms of this relationship. Furthermore, this study provides a constructive perspective on preventing and reducing academic burnout among college students.

Interactive effects of cumulative social-environmental risk and trait mindfulness on different types of adolescent mobile phone addiction

Interactive effects of cumulative social-environmental risk and trait mindfulness on different types of adolescent mobile phone addiction

Health and Health Care Use Strongly Associated with Cumulative Burden of Social Determinants of Health.

Understanding health outcomes and patterns of health care utilization associated with patients' cumulative social determinant of health (SDOH) risk is essential to supporting better health care. This study compared mental and physical health outcomes and health care utilization by increasing number of social needs among a clinical adult population. Surveys were sent to 6000 patients with recent visits to 7 primary care clinics in Portland, Oregon in 2018. The final study sample included respondents who matched to medical claims data, N = 1748. The authors used a modified logistic regression model to estimate risk ratios for the relationship between cumulative SDOH factors and self-reported chronic conditions, and a 2-part model to estimate the effects of cumulative SDOH risk on health care utilization. Increased SDOH need was associated with increasing likelihood of worse self-reported health outcomes, especially mental health. Compared with those with no SDOH need, having 1-2 SDOH need(s) (adjusted risk ratio [aRR] 1.25; 95% confidence interval [CI]: 1.06-1.46) and 3 or more SDOH needs (aRR 1.45; 95% CI: 1.22-1.73) had a greater risk of reporting any behavioral health condition. However, the number of SDOH had a graded but inverse impact on use of mental health care services where fewer visits were observed among those using care. Having SDOH was associated with increased likelihood of having an emergency department visit and increased number of primary care visits. This study demonstrates the compounding impact of SDOH on health and health care use. This highlights the importance of collecting SDOH, including the total number of SDOH needs, when considering a patient's health and health care.

Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population.

Nasopharyngeal carcinoma (NPC) and alcohol flush syndrome are thought to be strongly influenced by genetic factors and are highly prevalent amongst East Asians. Diminished activity of aldehyde dehydrogenase (ALDH), a major enzyme in the alcohol-metabolizing pathway, causes the flushing syndrome associated with alcoholic consumption. The genetic effect of ALDH isoforms on NPC is unknown. We therefore investigated the association between the genetic polymorphisms of all 19 ALDH isoforms and NPC among 458 patients with NPC and 1672 age- and gender-matched healthy controls in Taiwan. Single-nucleotide polymorphisms (SNPs) located between the 40,000 base pairs upstream and downstream of the 19 ALDH isoform coding regions were collected from two genome-wise association studies conducted in Taiwan and from the Taiwan Biobank. Thirteen SNPs located on ALDH4A1, ALDH18A1, ALDH3B2, ALDH1L2, ALDH1A2, and ALDH2 Glu487Lys (rs671) were associated with NPC susceptibility. Stratification by alcohol status revealed a cumulative risk effect for NPC amongst drinkers and non-drinkers, with odds ratios of 4.89 (95% confidence interval 2.15–11.08) and 3.57 (1.97–6.47), respectively. A synergistic effect was observed between SNPs and alcohol. This study is the first to report associations between genetic variants in 19 ALDH isoforms, their interaction with alcohol consumption and NPC in an East Asian population.

The long arm of childhood: The prolonged influence of adverse childhood experiences on depression during middle and old age in China.

Utilizing data from the nationally representative China Health and Retirement Longitudinal Study, this study analyzed the effect of intensity and duration of adverse childhood experiences on depression in middle aged and older aged adults in China. The mediating effect of cumulative health risk and personal factors were validated through the Karlson-Holm-Breen method. The results showed a significant dose-response relationship between adverse childhood experiences and adult depression. The elevated health risks of chronic diseases, disabilities, and physical pain, as well as the disadvantages in education, employment, and economic status caused by the adverse childhood experiences indirectly worsen adult depression.

Cumulative Ecological Risk and Problem Behaviors Among Adolescents in Secondary Vocational Schools: The Mediating Roles of Core Self-Evaluation and Basic Psychological Need Satisfaction.

Based on the Cumulative Risk Model, a single risk factor cannot play a decisive role, but the cumulative ecological risks may have complex superposition effects on adolescents' problem behaviors. However, although many studies have investigated the specific influences of single external risk factors on problem behaviors, the effect of cumulative ecological risk on problem behaviors and especially the underlying mechanisms therein have been under-investigated. Therefore, this study aimed to explore the effect of cumulative ecological risk on adolescents' problem behaviors, and the mediating effects of core self-evaluation and basic psychological needs satisfaction therein. To achieve this, 1,080 adolescents in secondary vocational schools were surveyed with the questionnaires of cumulative ecological risk, basic psychological need satisfaction, core self-evaluation, externalizing and internalizing problem behaviors. Results showed that: (a) cumulative ecological risk was positively related with both internalizing problem behavior and externalizing problem behavior; (b) core self-evaluation and basic psychological need satisfaction not only respectively but also sequentially mediated the relationship between cumulative ecological risk and two sorts of problem behaviors. These results provide some pivotal implications for the precaution and intervention of the adolescent problem behaviors.

Association between cumulative risk and protective factors with mental distress among female military spouses.

Guided by a resilience framework, this study examines the accumulation of risk and protective factors, as well as the potential buffering effects of protective factors on mental distress among female military spouses. Most research with this population has focused on individual risk factors affecting military spouses. Less frequently have the effects of cumulative risk, risk factors not specifically associated with military service, or protective factors been examined, though there is evidence for their importance. This study used secondary survey data from 334 female Army spouses collected in 2012 as part of the Land Combat Study 2. Cumulative risk and protective factor scores as well as scores within risk (intrapersonal, family, and military-specific) and protective (individual and environmental) factor domains were calculated. Four structural equation models were run to examine main and interaction effects on mental distress, a latent variable representing depression, anxiety, and trauma symptoms. In cumulative risk and protective factor models, cumulative risk was directly, positively associated with mental distress. This relationship was moderated by cumulative protection. In domain-specific models, only family risk was directly associated with mental distress. This relationship was moderated by environmental protective factors. Findings indicate mental distress among military spouses is associated with exposure to cumulative risk and attenuated by the presence of certain domains of protective factors. Family risk factors including marital distress and work-family conflict may be particularly pernicious stressors, but informal and structural supports may be important targets for prevention and intervention efforts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dyadic synchrony and repair processes are related to preschool children's risk exposure and self-control.

We examined associations between preschool children's cumulative risk exposure, dyadic interaction patterns, and self-control abilities in 238 mother-child dyads. Positive interactive synchrony, relationship ruptures, and latency to repair were micro-coded during a 3-5 minute joint challenge task. Children's self-control was assessed via two laboratory tasks and by parent report. Structural equation modeling and mediation analyses were utilized to examine the direct and indirect effects of cumulative risk on children's observed and parent-reported self-control abilities. Parent-child interactive processes of dyadic synchrony and latency to repair ruptures in synchrony were examined as mediators. Dyadic synchrony and latency to repair ruptures were found to mediate associations between cumulative risk exposure and children's behavioral and parent-reported self-control. Children exposed to more cumulative risk engaged in less dyadic synchrony and experienced longer latencies to repair ruptures with their caregiver, which in turn was associated with lower child self-control. Though cross-sectional, findings suggest dyadic synchrony and repair processes may represent viable mechanistic pathways linking cumulative risk exposure and deficits in child self-control. However, independent replications using longitudinal and experimental intervention designs are needed to determine causal pathways and inform new approaches for targeting the effects of early risk exposure through a focus on two-generational interventions.

Nonreceptor protein tyrosine phosphatases (NRPTPs) gene family associates with the risk of hepatocellular carcinoma in a Chinese hepatitis B virus-related subjects.

Nonreceptor protein tyrosine phosphatases (NRPTPs) are reported to be associated with several human cancers, but their roles in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. Here, we integrated bioinformatics tools, population association analyses, and biological assays to systematically screen for potentially functional single nucleotide polymorphisms (SNPs) within the 17 NRPTPs genes and evaluate the effects of candidate SNPs on the risk of HCC or persistent HBV infection. A total of 790 HBV-related HCC cases and 1454 cancer-free controls were enrolled. Controls included 711 HBV persistent carriers and 743 spontaneously recovered subjects. Results demonstrated that PTPN4 rs9308777 (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.06-1.49, P = .009) and PTPN12 rs350050 (OR = 1.26, 95% CI = 1.10-1.45, P = .001), were significantly associated with HCC risk, but not with persistent HBV infection risk. The cumulative risk effect of these two SNPs was more significantly increased the susceptibility to HCC (OR = 1.27, 95% CI = 1.14-1.41, P = 2.40 × 10-5 ). Subsequent biological assays further revealed the potential pathogenesis that PTPN4 rs9308777 might decrease the gene expression, and PTPN12 rs3750050 might promote cell proliferation by attenuating PTPN12's inhibitory activity on EGFR/ERK pathway. In summary, our integrative study highlights that PTPN4 and PTPN12 are significantly associated with HBV-related HCC risk, but do not influence persistent HBV infection. These findings shed light on the importance of the synergistic effects of regulatory and missense variants on the risk for HCC, and provide data to support personalized cancer medicine in the future.

S13. IMPACT OF POLYGENIC AND POLY-ENVIRONMENTAL RISK FACTORS ON A PSYCHOSIS RISK PHENOTYPE EXPLAINED THROUGH BRAIN STRUCTURE

BackgroundWhile single (genetic and environmental) risk factors for psychosis have been studied for their impact on brain structure and function, there is little understanding of how they interact to generate psychosis liability on the neural level. Direct associations between cumulative genetic risk scores and risk phenotypes are often weak, and analyses of G×E interactions are scarce. We developed and tested a multivariate model, in which the effects of cumulative environmental and genetic risk on a dimensional phenotype are mediated by brain structural variation.MethodsIn a data set of 440 non-clinical subjects, we tested a moderated mediation model with an interaction of an environmental (ERS) and a polygenic risk score (PRS) for schizophrenia, impacting on the subclinical psychosis spectrum phenotype schizotypy. We propose this effect to be mediated by grey matter volume variation, derived from voxel-based morphometry. In addition, cognitive function (CF) was considered as a potential moderator.ResultsFirstly, in a whole-brain analysis, we detected a significant interaction effect of PRS×ERS in a cluster (k=910, x/y/z=-4/-50/33, p=0.024 FWE cluster-level corrected) including the left precuneus (Pc, 64%) and posterior cingulate gyrus (pcG, 33%). Secondly, cluster values were extracted and entered into a multivariate moderated mediation model. This model was significant, showing that Pc/pcG volume mediated the impact of a PRS×ERS interaction on positive schizotypy (R2=10.91%, p=4.9×10–5). In predicting Pc/pcG variation (R2=51.69%), neither PRS (b=0.638, p=0.830) nor ERS had a main effect on grey matter variation, but their interaction was significant (b=-3.13, p=0.002): The intensity and direction of the PRS effect is moderated by the level of ERS, with a positive slope for low ERS (i.e., low environmental risk), and a negative slope for high ERS. In predicting positive schizotypy, the direct effects of PRS (b=6.116, p=0.477) and ERS (b=0.006, p=0.068) were not significant. However, we demonstrate an indirect effect through brain structural variation, showing a significant mediation (index=0.223, bootstrapped confidence interval 0.004–0.542). Cluster variation had a significant main effect on positive schizotypy (b=-0.277, p=0.049), but was modulated by the level of cognitive function, with a positive slope for low CF, and a negative slope for high CF, showing a second significant interaction (b=-0.070, p=0.027).DiscussionOur finding is the first to integrate polygenic and poly-environmental markers with MRI parameters to demonstrate that the interaction of these cumulated risk factors leads to the emergence of subclinical symptoms through changes in brain structure. Furthermore, our model confirms cognition as a protective factor, indicating that above-average levels of cognitive function can compensate for dysfunctional processes that arise from altered neurodevelopment. Such compensatory mechanisms are crucial for understanding resilience, explaining high (positive) symptom load in unaffected individuals. Conventional diathesis-stress models propose increased vulnerability specifically to adverse events – our model extends this to suggest an inverted effect for high PRS and low ERS subjects. Under favourable environmental conditions, an increased genetic load might paradoxically result in low psychopathology outcomes or gain of function, supporting the notion of genes associated with schizophrenia as “plasticity genes” rather than simple risk factors. In sum, the present study provides proof for a multivariate model predicting the impact of genetic and environmental risk on a psychosis risk phenotype, extendable to other clinical spectra.