Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development.

BACKGROUND: Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene-environment interaction using a polygenic risk score for depression (PRS-depression) in the context of peer victimisation and depressive symptoms in adolescence. METHODS: The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12-13 years) obtained from both self- and teacher-reports, as well as self-reported depressive symptoms (15-17 years). The PRS-depression was based on the genome-wide association meta-analysis of broad depression by Howard et al. (2019). RESULTS: Self- and teacher-reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (ß = 0.34, p < .001; ß = 0.14, p = .001 respectively), and this association remained significant when accounting for PRS-depression (ß = 0.33, p < .001; ß = 0.13, p = .002 respectively). PRS-depression was independently associated with depressive symptoms, but there was no significant PRS-depression by peer victimisation interaction (self-reported and teacher-reported). PRS-depression was correlated with self-reported, but not teacher-reported, peer victimisation. CONCLUSIONS: Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS-depression, and being exposed to peer victimisation (self- and teacher-reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS-depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene-environment correlation between PRS-depression and self-reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation.

Comparison of saliva with oral and nasopharyngeal swabs for SARS-CoV-2 detection on various commercial and laboratory-developed assays.

The accurate laboratory detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a crucial element in the fight against coronavirus disease 2019 (COVID-19). Reverse transcription-polymerase chain reaction testing on combined oral and nasopharyngeal swab (ONPS) suffers from several limitations, including the need for qualified personnel, the discomfort caused by invasive nasopharyngeal sample collection, and the possibility of swab and transport media shortage. Testing on saliva would represent an advancement. The aim of this study was to compare the concordance between saliva samples and ONPS for the detection of SARS-CoV-2 on various commercial and laboratory-developed tests (LDT). Individuals were recruited from eight institutions in Quebec, Canada, if they had SARS-CoV-2 RNA detected on a recently collected ONPS, and accepted to provide another ONPS, paired with saliva. Assays available in the different laboratories (Abbott RealTime SARS-CoV-2, Cobas® SARS-CoV-2, Simplexa™ COVID-19 Direct, Allplex™ 2019-nCoV, RIDA®GENE SARS-CoV-2, and an LDT preceded by three different extraction methods) were used to determine the concordance between saliva and ONPS results. Overall, 320 tests were run from a total of 125 saliva and ONPS sample pairs. All assays yielded similar sensitivity when saliva was compared to ONPS, with the exception of one LDT (67% vs. 93%). The mean difference in cycle threshold (∆C t ) was generally (but not significantly) in favor of the ONPS for all nucleic acid amplification tests. The maximum mean ∆​​​​​C t was 2.0, while individual ∆C t varied importantly from -17.5 to 12.4. Saliva seems to be associated with sensitivity similar to ONPS for the detection of SARS-CoV-2 by various assays.

Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population-representative longitudinal birth cohort.

Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively-measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7-26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The life-course-persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions.

Cumulative risk and protection effect of serotonergic genes on male antisocial behaviour: results from a prospective cohort assessed in adolescence and early adulthood.

BACKGROUND: Heritability of antisocial behaviour is estimated at approximately 50% and involves multiple genes.AimsTo investigate the cumulative genetic effects of 116 single nucleotide polymorphisms mapping to 11 candidate serotonergic genes and antisocial behaviours, in adolescence and in early adulthood. METHOD: Participants were 410 male members of the Quebec Longitudinal Study of Kindergarten Children, a population-based cohort followed up prospectively from age 6 to age 23. The serotonergic genes were selected based on known physiological processes and prior associations with antisocial behaviours. Antisocial behaviours were self-reported and assessed by using semi-structured interviews in adolescence and in adulthood. RESULTS: Cumulative, haplotype-based contributions of serotonergic genes conferring risk and protection for antisocial behaviours were detected by using multilocus genetic profile risk scores (MGPRSs) and multilocus genetic profile protection scores (MGPPSs). Cumulatively, haplotype-based MGPRSs and MGPPSs contributed to 9.6, 8.5 and 15.2% of the variance in general delinquency in adolescence, property/violent crimes in early adulthood and physical partner violence in early adulthood, respectively. CONCLUSIONS: This study extends previous research by showing a cumulative effect of multiple haplotypes conferring risk and protection to antisocial behaviours in adolescence and early adulthood. The findings further support the relevance of concomitantly considering multiple serotonergic polymorphisms to better understand the genetic aetiology of antisocial behaviours. Future studies should investigate the interplay between risk and protective haplotype-based multilocus genetic profile scores with the environment. DECLARATION OF INTEREST: I.O.-M. holds a Canada Research Chair in the developmental origins of vulnerability and resilience.

Enduring effect of childhood maltreatment on cortisol and heart rate responses to stress: The moderating role of severity of experiences.

There is a relative consensus about the detrimental impact of childhood maltreatment on later mental health problems and behavioral difficulties. Prior research suggests that neurophysiological stress mechanisms may partly mediate this association. However, inconsistent findings regarding hypothalamic-pituitary-adrenal axis and sympathetic responses to stress complicate this investigation. Furthermore, the concordance in these two stress systems is not well understood. We tested whether the severity of maltreatment affected the association between maltreatment and cortisol and heart rate (HR) stress responses and the symmetry of these responses. Participants were 155 males (56 maltreated and 99 controls) aged 18 to 35 years. Cortisol and HR were measured in response to the Trier Social Stress Test. Childhood maltreatment, sociodemographic factors, and health-related factors were measured using self-reported questionnaires. Maltreated participants had higher cortisol responses to stress in comparison to controls. However, a shift from moderate to lower to higher cortisol responses was noted as the severity of the experiences increased. Participants exposed to more experiences of maltreatment also showed a greater symmetry between cortisol and HR stress responses. Our findings provide further support for persistent dysregulation of the HPA axis following childhood maltreatment, of which the expression and symmetry with the sympathetic system may change according to the severity of experiences.

Comprehensive analysis of the specificity of transcription activator-like effector nucleases.

A key issue when designing and using DNA-targeting nucleases is specificity. Ideally, an optimal DNA-targeting tool has only one recognition site within a genomic sequence. In practice, however, almost all designer nucleases available today can accommodate one to several mutations within their target site. The ability to predict the specificity of targeting is thus highly desirable. Here, we describe the first comprehensive experimental study focused on the specificity of the four commonly used repeat variable diresidues (RVDs; NI:A, HD:C, NN:G and NG:T) incorporated in transcription activator-like effector nucleases (TALEN). The analysis of >15 500 unique TALEN/DNA cleavage profiles allowed us to monitor the specificity gradient of the RVDs along a TALEN/DNA binding array and to present a specificity scoring matrix for RVD/nucleotide association. Furthermore, we report that TALEN can only accommodate a relatively small number of position-dependent mismatches while maintaining a detectable activity at endogenous loci in vivo, demonstrating the high specificity of these molecular tools. We thus envision that the results we provide will allow for more deliberate choices of DNA binding arrays and/or DNA targets, extending our engineering capabilities.

Quality Assurance and Prevention of COVID-19 Before Admission in Geriatric Rehabilitation Unit in Long-Term Care Facilities.

Background: This quality assurance study was conducted during the COVID-19 pandemic to describe the profile of patients aged 65 years and older admitted to a transition unit in a long-term care (LTC) facility and to evaluate the impact of admission modalities, compliance with screening and hand hygiene practices, risk of COVID-19, and time to access a geriatric rehabilitation unit (GRU). Methods: A prospective study was conducted using administrative and medical records from three Montreal public LTC facilities offering a rehabilitation program for 312 patients admitted between May 2020 and February 2021. The results are reported for the entire sample and compared according to the mode of admission. Results: The incidence of COVID-19 during the transition unit stay was estimated to be 11 cases or 3.5% in 14 days. Assessment of screening compliance showed deficiencies for 41.3% of patients, and the frequency of hand hygiene audits was not strictly adhered to. More COVID-19 cases were recorded in patients admitted to the transition unit by bed availability than in the cohort mode. The time to access a rehabilitation unit was 7.2 days or 23.5% shorter for patients admitted by bed availability. Conclusions: The study, conducted from a continuous practice improvement perspective, showed that the implementation of a transition unit in the LTC facilities helped control the transmission of COVID-19, but also revealed flaws in screening and hand hygiene practices.

Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/µl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/µl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/µl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

Genetic associations with parental investment from conception to wealth inheritance in six cohorts.

Genetic inheritance is not the only way parents' genes may affect children. It is also possible that parents' genes are associated with investments into children's development. We examined evidence for links between parental genetics and parental investments, from the prenatal period through to adulthood, using data from six population-based cohorts in the UK, US and New Zealand, together totalling 36,566 parents. Our findings revealed associations between parental genetics-summarized in a genome-wide polygenic score-and parental behaviour across development, from smoking in pregnancy, breastfeeding in infancy, parenting in childhood and adolescence, to leaving a wealth inheritance to adult children. Effect sizes tended to be small at any given time point, ranging from RR = 1.12 (95% confidence interval (95%CI) 1.09, 1.15) to RR = 0.76 (95%CI 0.72, 0.80) during the prenatal period and infancy; ß = 0.07 (95%CI 0.04, 0.11) to ß = 0.29 (95%CI 0.27, 0.32) in childhood and adolescence, and RR = 1.04 (95%CI 1.01, 1.06) to RR = 1.11 (95%CI 1.07, 1.15) in adulthood. There was evidence for accumulating effects across development, ranging from ß = 0.15 (95%CI 0.11, 0.18) to ß = 0.23 (95%CI 0.16, 0.29) depending on cohort. Our findings are consistent with the interpretation that parents pass on advantages to offspring not only via direct genetic transmission or purely environmental paths, but also via genetic associations with parental investment from conception to wealth inheritance.

A multi-informant and multi-polygenic approach to understanding predictors of peer victimisation in childhood and adolescence.

Introduction: Peer victimisation is a prevalent occurrence in childhood and adolescence and can often have long-lasting consequences. Previous research using polygenic scores (PGSs) have revealed various genetic vulnerabilities as predictive of victimisation in childhood. However, findings were based on self-report and may therefore be influenced by varying self-perceptions. Previous investigations also focused on average victimisation across childhood, and thus do not capture variability in polygenic predictability over time. The present study, therefore, aimed to investigate associations between PGSs and victimisation using separate and combined reports from teachers and peers in childhood, as well as self-reports in later adolescence to explore trajectories of victimisation. Methods: Data were derived from the Quebec Newborn Twin Study. Participants were assessed for victimisation using self-reports from 7 to 17 years and using teacher ratings and peer nominations between 7 and 10 years (n = 536). Ten PGSs related to mental health, cognitive abilities and physical traits were examined as possible predictors of victimisation using linear regressions and growth curve models. Results: Findings revealed that PGSs associated with victimisation are consistent across informants, but to varying extent according to estimated effect sizes. Self-reported victimisation was predicted by PGSs related to mental health, while PGSs related to cognitive and physical traits had larger effect estimates when predicting teacher- and peer-reported victimisation. The PGS for educational attainment was consistently negatively associated with victimisation across informants, producing the largest effect estimates (ß = -.104, 95% CI = -.169 to -.039) when predicting a multi-informant measure of victimisation. No PGS predicted changes in victimisation over time. Conclusion: While the PGS for educational attainment is a robust predictor of victimisation, many PGSs are differentially associated with victimisation depending on the informant. Such findings highlight the need to pay close attention to the phenotypic assessment of victimisation, and show that using multiple informants can both strengthen and provide unique insight into how associations may occur.

Life-Course Persistent Antisocial Behavior and Accelerated Biological Aging in a Longitudinal Birth Cohort.

Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N = 1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (ß, 0.22, 95%CI, 0.14, 0.28, p ≤ 0.001). This amounted to 4.3 extra years of biological aging between ages 25-45 years for Study members following the LCP trajectory compared to low-antisocial trajectory individuals. LCP offenders also experienced more midlife difficulties with hearing (ß, -0.14, 95%CI, -0.21, -0.08, p ≤ 0.001), balance (ß, -0.13, 95%CI, -0.18, -0.06, p ≤ 0.001), gait speed (ß, -0.18, 95%CI, -0.24, -0.10, p ≤ 0.001), and cognitive functioning (ß, -0.25, 95%CI, -0.31, -0.18, p ≤ 0.001). Associations represented a decline from childhood health. Associations persisted after controlling individually for tobacco smoking, antipsychotic medication use, midlife illnesses, maltreatment, socioeconomic status, incarceration, and childhood self-control difficulties. However, the cumulative effect of these lifestyle characteristics together explained why LCP offenders have a faster Pace of Aging than their peers. While older adults typically age-out of crime, LCP offenders will likely age-into the healthcare system earlier than their chronologically same-aged peers. Preventing young people from offending is likely to have substantial benefits for health, and people engaging in a LCP trajectory of antisocial behaviors might be the most in need of health promotion programs. We offer prevention and intervention strategies to reduce the financial burden of offenders on healthcare systems and improve their wellbeing.

First case of invasive human infection caused by Cupriavidus metallidurans.

We describe the first case of invasive human infection (a nosocomial septicemia) caused by Cupriavidus metallidurans. This metal-resistant bacterium has not been reported to be pathogenic in humans or animals.

Impact of maltreatment on depressive symptoms in young male adults: The mediating and moderating role of cortisol stress response and coping strategies.

BACKGROUND: Converging evidence suggests that maltreated children suffer from depression at an early age and experience recurrent episodes of depression that persist over longer periods of time. However, the stress-related mechanisms hypothesized to be implicated in these associations remain to be specified. The present study tested the mediating and moderating roles of acute cortisol response to stress and coping strategies in the association between child maltreatment and depressive symptoms in early adulthood. METHODS: Data from 156 men aged 18 to 35 years (n = 56 maltreated) were collected using self-reported questionnaires assessing child maltreatment, depressive symptomatology and coping strategies. Cortisol was measured in response to the "Trier Social Stress Test" (TSST). RESULTS: Although acute cortisol response to stress did not mediate the maltreatment-depressive symptoms association, a moderation effect was found. Child maltreatment was associated with higher risk of depressive symptoms among participants with a higher cortisol response to stress, but not for those with moderate-to-lower cortisol responses. Additionally, maltreated participants reported more depressive symptoms, an association that was partly explained by their higher use of emotion-oriented coping (mediation). Finally, maltreated individuals who reported using less task-oriented coping had greater depressive symptomatology than those who adopted this coping strategy more frequently (moderation). CONCLUSION: These findings extend prior work examining the role of the hypothalamic-pituitary-adrenal (HPA) axis in the etiology of depression. The results draw attention to coping strategies, in addition to acute cortisol response to stress, as potential targets for mitigating the onset of depressive symptoms in adults maltreated as children.

Sexual Aggressors Against Women's Sexual Lives: A Latent Class Analysis.

This study investigated the day-to-day deviant and nondeviant sexuality of a sample of Canadian sexual aggressors against women ( N = 160). Using latent class analysis, three latent classes were identified: internalized deviant (ID), low sexual problem (LSP), and hypersexual deviant (HD). Following the latent class analysis, the developmental, physiological, cognitive, and criminological correlates of these lifestyles were analyzed. ID ( n = 31) aggressors were characterized by sexual dissatisfaction, sexual deviance, and a bland sexual life. LSP ( n = 116) aggressors were characterized by the absence of sexual deviance or hypersexuality. HD ( n = 13) aggressors were characterized by hypersexuality and sexual deviance. Our exploratory study suggests that the day-to-day nondeviant and deviant sexual life of sexual aggressors against women appear to affect their modus operandi. Furthermore, the adult sexual lifestyles of sexual aggressors against women appear to be extensions of their adolescent sexual lifestyles. The results of this study thus suggest avenues for research-notably, the specific influence of sexual behaviours and internalized psychosexual problems on modus operandi-that could improve the clinical management of sexual aggressors against women.

A case of Japanese encephalitis virus infection acquired during a trip in Thailand.

A case of Japanese encephalitis virus (JEV) infection is reported in a young traveler returning from Thailand. Clinical suspicion of JEV in travelers returning from endemic areas with neurologic symptoms is warranted. Confirmation of the diagnosis is complex and requires specialized laboratory services. Individualized advice on the costs and benefits of vaccination is recommended.

A strategy to retrieve the whole set of protein modules in microbial proteomes.

Protein homology is often limited to long structural segments that we have previously called modules. We describe here a suite of programs used to catalog the whole set of modules present in microbial proteomes. First, the Darwin AllAll program detects homologous segments using thresholds for evolutionary distance and alignment length, and another program classifies these modules. After assembling these homologous modules in families, we further group families which are related by a chain of neighboring unrelated homologous modules. With the automatic analysis of these groups of families sharing homologous modules in independent multimodular proteins, one can split into their component parts many fused modules and/or deduce by logic more distant modules. All detected and inferred modules are reassembled in refined families. These two last steps are made by a unique program. Eventually, the soundness of the data obtained by this experimental approach is checked using independent tests. To illustrate this modular approach, we compared four proteobacterial proteomes (Campylobacter jejuni, Escherichia coli, Haemophilus influenzae, and Helicobacter pylori). It appears that this method might retrieve from present-day proteins many of the modules which can help to trace back ancient events of gene duplication and/or fusion.