Patterns of resilient functioning in early life: Identifying distinct groups and associated factors.

Resilience, the capacity to maintain or regain functionality in the face of adversity, is a dynamic process influenced by individual, familial, and community factors. Despite its variability, distinct resilience trajectories can be identified within populations, yet the predictors defining these distinct groups remains largely unclear. Here, using data from the Avon Longitudinal Study of Parents and Children (ages 0-18), we quantify resilience as the remaining variance in psychosocial functioning after taking into account the exposure to adversity. Growth mixture modeling identified seven distinct resilience trajectories, with over half of the study population maintaining resilience throughout early life. Factors increasing the likelihood of resilient trajectory membership included a less emotional temperament, high cognitive abilities, high self-esteem, low levels of autistic social traits, strong sibling relationships, high maternal care, and positive school experiences. Among the socioeconomic factors considered, maternal education - a significant indicator of socioeconomic status - and birth-order were associated with resilient trajectories. Our findings underscore the importance of fostering cognitive abilities, self-esteem, social relationships, positive school experiences, and extracurricular engagement to bolster resilience in adversity-exposed individuals and communities. This research informs resilience-focused interventions in mental health, education, and social policy sectors, and prompts further exploration of socioeconomic influences on resilience trajectories.

The effect of adverse and positive experiences on inflammatory markers in Australian and UK children.

Background: The relationship between childhood adversity and inflammation is well-established. Examination of positive experiences can provide a more complete understanding of intervention opportunities. We investigated associations of adverse and positive experiences, and their intersection, with inflammation in children and adolescents. Methods: Data sources: Longitudinal Study of Australian Children (LSAC; N = 1237) and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3488). Exposures: Adverse and positive experiences assessed repeatedly (LSAC: 0-11 years; ALSPAC: 0-15 years). Outcomes: Inflammation quantified by high sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Analyses: Linear regression on the log-transformed outcomes estimated the relative difference in inflammatory markers with adverse/positive experiences, adjusting for socio-demographics and concurrent positive/adverse experiences, respectively. Results: Most associations were in the expected direction but differed in magnitude by exposure, outcome and cohort. Across both cohorts, adverse experiences were associated with up to 7.3% higher hsCRP (95% CI: -18.6%, 33.2%) and up to 2.0% higher GlycA (95% CI: 0.5%, 3.5%); while positive experiences were associated with up to 22.1% lower hsCRP (95% CI: -49.0%, 4.7%) and 1.3% lower GlycA (95% CI: -2.7%, 0.2%). In LSAC, the beneficial effect of positive experiences on inflammation was more pronounced among those with fewer concurrent adverse experiences. Conclusion: Across two cohorts, we found small but directionally consistent associations between adverse experiences and higher inflammation, and positive experiences and lower inflammation, particularly for GlycA. Future research should give further consideration to positive experiences to complement the current focus on adversity and inform the design and evaluation of early life interventions.

Genetic Variants Associated With Resilience in Human and Animal Studies.

Resilience is broadly defined as the ability to maintain or regain functioning in the face of adversity and is influenced by both environmental and genetic factors. The identification of specific genetic factors and their biological pathways underpinning resilient functioning can help in the identification of common key factors, but heterogeneities in the operationalisation of resilience have hampered advances. We conducted a systematic review of genetic variants associated with resilience to enable the identification of general resilience mechanisms. We adopted broad inclusion criteria for the definition of resilience to capture both human and animal model studies, which use a wide range of resilience definitions and measure very different outcomes. Analyzing 158 studies, we found 71 candidate genes associated with resilience. OPRM1 (Opioid receptor mu 1), NPY (neuropeptide Y), CACNA1C (calcium voltage-gated channel subunit alpha1 C), DCC (deleted in colorectal carcinoma), and FKBP5 (FKBP prolyl isomerase 5) had both animal and human variants associated with resilience, supporting the idea of shared biological pathways. Further, for OPRM1, OXTR (oxytocin receptor), CRHR1 (corticotropin-releasing hormone receptor 1), COMT (catechol-O-methyltransferase), BDNF (brain-derived neurotrophic factor), APOE (apolipoprotein E), and SLC6A4 (solute carrier family 6 member 4), the same allele was associated with resilience across divergent resilience definitions, which suggests these genes may therefore provide a starting point for further research examining commonality in resilience pathways.

The validity of the residuals approach to measuring resilience to adverse childhood experiences.

BACKGROUND: Resilience is broadly defined as the ability to maintain or regain functioning in the face of adversity. Recent work to harmonise the quantification and definition of resilience quantifies resilience as the residual variance in psychosocial functioning that remains after accounting for adversity exposure. However, there have been no published studies that have formally investigated the validity of this approach. Considering this, we examine the construct and predictive validity of the residuals approach using participants from the Avon Longitudinal Study of Parents and Children (ALSPAC), a multigenerational, longitudinal cohort study. METHODS: We regressed exposures of adolescent adversity on adolescent psychopathology scores using the Strength and Difficulties Questionnaire and obtained the residual variance. We investigated construct validity by analysing whether previously identified demographic and resilience factors significantly predicted resilience. Predictive validity of resilience was investigated by comparing the predictive power of resilience with other determinants of psychosocial functioning on two developmental outcomes: depressive symptoms at 18 years, measured by the Short Moods and Feelings Questionnaire, and NEET (Not in Employment, Education or Training) status at 17 and 23 years. The associations between depressive symptoms at 18, resilience, ACEs and covariates were tested using multiple linear regression. NEET status at 17 and 23 were run as separate binary multiple logistic regression models to test associations with resilience and known demographics previously associated with NEET status. RESULTS: Seven previously identified protective factors, including self-esteem, positive sibling relationship, temperament, and positive perception of school, significantly predicted resilience to adolescent psychopathology, thus providing strong construct validity. Resilience significantly predicted a reduction in depressive symptoms at 18 years, and significantly decreased the likelihood of having NEET status at both 17 years and 23 years, even after taking into account early childhood adversity and other risk factors. None of the socioeconomic factors were significantly associated with resilience. CONCLUSIONS: Our study demonstrates that the residuals method of operationalising resilience has good construct and predictive validity yet recommend replication studies. It has the potential to advance research into the mechanisms and modifiability of resilience. TRIAL REGISTRATION: Not applicable.

In vitro evaluation of Sensi-IP®: A soluble and mineralizing sensitivity solution.

OBJECTIVES: Sensi-IP®OG (SIP-OG) and Sensi-IP®FF (SIP-FF) are soluble bioactive glasses developed to treat dentin hypersensitivity and promote remineralization. Evaluation of their therapeutic potential to reduce dentin hypersensitivity and recover enamel strength was evaluated using standardized in vitro assessments based on simulated use. METHODS: To assess dentin occlusion a visual occlusion methodology was employed. Dentin discs were subjected to twice-daily simulated brushing (for 5 days) using 0.67 g of toothpaste for 10 s. Simple prototype toothpastes containing SIP-OG and SIP-FF were compared to commercially available controls: Colgate® Sensitive Pro-Relief (CPR) and Sensodyne® Repair and Protect with NovaMin® (SRP). Samples were stored in artificial saliva between treatments. All samples were assessed at baseline and subsequent to each treatment and were scored on a 5-point categorical scale for occlusion. For enamel surface effects, test articles of SIP-OG, SIP-FF, and SIP-FF with NaF were compared to a positive (with NaF) and a negative (no NaF) control paste. Enamel samples were subjected to a pH cycling regime, providing exposure to the toothpaste slurry (i.e., 2 parts deionized water to 1 part toothpaste), mineralizing solution, and demineralizing solution over 5 days of simulated use. Samples were stored overnight in mineralizing solution. Samples were evaluated for fluoride uptake and changes to surface microhardness. RESULTS: Visual occlusion scores (1 fully occluded to 5 unoccluded) were 2.6, 3.8, 4.4 and 4.0 after 1 day of simulated use for SIP-OG, SIP-FF with NaF, Colgate® Sensitive Pro-Relief and Sensodyne® Repair and Protect, respectively, decreasing to 1.0, 1.8, 3.1 and 3.9 after 5 days of application. SIP-OG provided superior occlusion at the significance level of p ≤ 0.05 at 1, 2, 3, 4, and 5 days. SIP-FF with NaF provided superior occlusion at the significance level of p ≤ 0.05 at 2, 4, and 5 days. Fluoride uptake ranged from 9.0 µg/cm2 for SIP-OG to 12.4 µg/cm2 for SIP-FF with NaF. Surface microhardness after acid cycling allowed recovery of 59 % of surface microhardness after treatment with SIP-OG or SIP-FF with NaF. SIP-OG achieved significant surface microhardness recovery versus SIP-FF alone, a NaF control paste, and a fluoride free control paste at the significance level of p ≤ 0.05. SIP-FF with NaF achieved surface microhardness recovery versus SIP-FF alone, a NaF control paste, and a fluoride free control paste at the significance level of p ≤ 0.05. CONCLUSIONS: Superior occlusion of dentin tubules was observed with both novel additives compared to commercially available toothpastes. A build-up effect with increasing occlusion was noted with repeated application for both novel additives and ascribed to mineralization effects, as supported by surface microhardness recovery on initial enamel lesions.

A Cross-Species Systems Genetics Analysis Links APBB1IP as a Candidate for Schizophrenia and Prepulse Inhibition.

Background: Prepulse inhibition (PPI) of the startle response is a highly conserved form of sensorimotor gating, disruption of which is found in schizophrenia patients and their unaffected first-degree relatives. PPI can be measured in many species, and shows considerable phenotypic variation between and within rodent models. This makes PPI a useful endophenotype. Genome-wide association studies (GWAS) have been carried out to identify genetic variants underlying schizophrenia, and these suggest that schizophrenia is highly polygenic. GWAS have been unable to account for the high heritability of schizophrenia seen in family studies, partly because of the low power of GWAS due to multiple comparisons. By contrast, complementary mouse model linkage studies often have high statistical power to detect variants for behavioral traits but lower resolution, producing loci that include tens or hundreds of genes. To capitalize on the advantages of both GWAS and genetic mouse models, our study uses a cross-species approach to identify novel genes associated with PPI regulation, which thus may contribute to the PPI deficits seen in schizophrenia. Results: Using experimental data from the recombinant inbred (RI) mouse panel BXD, we identified two significant loci affecting PPI. These genomic regions contain genetic variants which influence PPI in mice and are therefore candidates that may be influencing aspects of schizophrenia in humans. We next investigated these regions in whole-genome data from the Psychiatric Genomics Consortium (PGC) schizophrenia GWAS and identify one novel candidate gene (ABPP1IP) that was significantly associated with PPI in mice and risk of schizophrenia in humans. A systems genetics approach demonstrates that APBB1IP coexpresses with several other genes related to schizophrenia in several brain regions. Gene coexpression and enrichment analysis shows clear links between APBB1IP and the immune system. Conclusion: The combination of human GWAS and mouse quantitative trait loci (QTL) from some of the largest study systems available has enabled us to identify a novel gene, APBB1IP, which influences schizophrenia in humans and PPI in mice.