Louise Arseneault

• PhD Biomedical Sciences
• Professor at King's College London

This study tests the association of whole-blood DNA methylation and antidepressant exposure in 16,531 individuals from Generation Scotland (GS), using self-report and prescription-derived measures. We identify 8 associations and a high concordance of results between self-report and prescription-derived measures. Sex-stratified analyses observe nomi...

Polygenic score (PGS) predictions of educational achievement are sizeable at population level. They capture so-called ‘direct’ genetic effects that are independent of environmental confounding, but also ‘indirect’ genetic effects due to gene-environment correlations, assortative mating, and population stratification. Indirect genetic effects compli...

Nursery rhymes are rich in alliteration and vocabulary, and their benefits for children’s language and literacy have been widely studied. Less is known about the influence that nursery rhymes’ messages may have on children’s development. Here, we focused on ‘Monday’s Child’, a popular nursery rhyme which alleges that the day of the week of children...

Background Adverse childhood experiences (ACEs) are associated with mental health problems, but many children who experience ACEs do not develop such difficulties. A warm and supportive adult presence in childhood is associated with a lower likelihood of developing mental health problems after exposure to ACEs. However, it is unclear whether this a...

Aims Exposure to multiple forms of victimisation in childhood (often referred to as poly-victimisation) has lifelong adverse effects, including an elevated risk of early-adulthood psychopathology. However, not all poly-victimised children develop mental health difficulties and identifying what protects them could inform preventive interventions. Th...

We assessed genetic and environmental influences on social isolation across childhood and the overlap between social isolation and mental health symptoms including depression symptoms, conduct problems, and psychotic-like experiences from adolescence to young adulthood. Participants included 2,232 children from the Environmental Risk Longitudinal T...

Bullying behaviors and conduct problems are two forms of antisocial behavior that frequently co-occur in childhood. However, it remains unclear whether their developmental trajectories are distinct and the extent to which different aspects of cognitive functioning account for their development. We aimed to disentangle the developmental trajectories...

Importance: Understanding antidepressant mechanisms could help design more effective and tolerated treatments. Objective: Identify DNA methylation (DNAm) changes associated with antidepressant exposure. Design: Case-control methylome-wide association studies (MWAS) of antidepressant exposure were performed from blood samples collected between 2006-...

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder for which genetic factors explain up to 75% of the variance. In this study, we performed a genome-wide association meta-analysis (GWAMA) of ADHD symptom measures, with an effective sample size of 120,092 (71,733 unique individuals from 28 population-based coh...

Background Adverse childhood experiences (ACEs) are well‐established risk factors for self‐harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co‐occurring self‐harm and depression. Methods Data were utilised from over 22,000 childre...

The negative health consequences of loneliness have led to increasing concern about the economic cost of loneliness in recent years. Loneliness may also incur an economic burden more directly, by impacting socioeconomic position. Much of the research to date has focused on employment status which may not fully capture socioeconomic position and has...

Background Loneliness is a risk factor for a range of mental and physical health problems and has gained increasing interest from policy-makers and researchers in recent years. However, little attention has been paid to loneliness at work and its implications for workers and employers. Aims Identify workplace, health and personal factors associate...

Major Depression (MD) is a leading cause of global disease burden, and both experimental and population-based studies suggest that differences in DNA methylation (DNAm) may be associated with the condition. However, previous DNAm studies have not so far been widely replicated, suggesting a need for larger meta-analysis studies. In the present study...

Importance Understanding which children in the general population are at greatest risk of poor functional outcomes could improve early screening and intervention strategies. Objective To investigate the odds of poor outcomes in emerging adulthood (ages 17 to 20 years) for children with different mental health trajectories at ages 9 to 13 years. D...

Introduction Social isolation in childhood can be detrimental to physical and mental health. Children with neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD), may be particularly at risk for becoming socially isolated. Similarly, isolated children have limited opportunities to observe, model, and learn age-appropr...

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 cohort...

Background Emotional symptoms, such as anxiety and depressive symptoms, are common during adolescence, often persist over time, and can precede the emergence of severe anxiety and depressive disorders. Studies suggest that a vicious cycle of reciprocal influences between emotional symptoms and interpersonal difficulties may explain why some adolesc...

Study objectives: Digital technology use is associated with poor sleep quality in adolescence and young adulthood although research findings have been mixed. No studies have addressed the association between the two using a genetically informative twin design which could extend our understanding of the etiology of this relationship. This study aim...

Objectives: Individuals with more education are at lower risk of developing multiple, different age-related diseases than their less educated peers. A reason for this might be that individuals with more education age slower. There are two complications in testing this hypothesis. First, there exists no definitive measure of biological aging. Secon...

Background and hypothesis: Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not bee...

Objective: This study examined longitudinal associations between attention-deficit/hyperactivity disorder (ADHD) symptoms and social isolation across childhood. The study tested the direction of this association across time, while accounting for preexisting characteristics, and assessed whether this association varied by ADHD presentation, informa...

Purpose Violence occurs at multiple ecological levels and can harm mental health. However, studies of adolescents’ experience of violence have often ignored the community context of violence, and vice versa. We examined how personal experience of severe physical violence and living in areas with high levels of neighbourhood disorder during adolesce...

Objective: We investigated whether “late-onset” ADHD that emerges in adolescence/adulthood is similar in risk factor profile to: (1) child-onset ADHD, but emerges later because of scaffolding/compensation from childhood resources; and (2) depression, because it typically onsets in adolescence/adulthood and shows symptom and genetic overlaps with AD...

Background: Chaotic home environments may contribute to children's attention-deficit hyperactivity disorder (ADHD) symptoms. However, ADHD genetic risk may also influence household chaos. This study investigated whether children in chaotic households had more ADHD symptoms, if mothers and children with higher ADHD genetic risk lived in more chaoti...

Background: This study examined early life antecedents of childhood social isolation, whether these factors accounted for poor outcomes of isolated children, and how these associations varied according to patterns of stability and change in childhood isolation. Methods: Participants included 2232 children from the Environmental Risk (E-Risk) Lon...

Background: Trajectories of attention-deficit hyperactivity disorder (ADHD) traits spanning early childhood to mid-life have not been described in general populations across different geographical contexts. Population trajectories are crucial to better understanding typical developmental patterns. Methods: We combined repeated assessments of ADH...

Background Bullying victimisation has been associated with increased risk of suicide ideation and attempt throughout the lifespan, but no study has yet examined whether it translates to a greater risk of death by suicide. We aimed to determine the association of bullying victimisation with suicide mortality. Methods Participants were drawn from th...

The present study examined patterns of stability and change in loneliness across adolescence. Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative cohort of 2,232 individuals born in 1994 and 1995. Loneliness was assessed when participants were aged 12 and 18. Loneliness showed modest stabilit...

Background: Loneliness co-occurs alongside many mental health problems and is associated with poorer treatment outcomes. It could therefore be a phenomenon of interest to clinicians as an indicator of generalised risk for psychopathology. The present study tested whether a short measure of loneliness can accurately classify individuals who are at...

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al. 2020). Here we report a next-generation DNA-methyl...

Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity – a risk factor for MDD – becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigatio...

Purpose To investigate whether (1) depression is associated with increased risk of past-year intimate partner violence (IPV) perpetration, disaggregated by sex, after controlling for potential confounders; (2) observed associations are mediated by alcohol misuse or past-year IPV victimisation. Methods Systematic review and individual participant d...

Purpose Bullying behaviours and other conduct problems often co-occur. However, we do not yet know whether bullying behaviours are associated with early factors and later poor outcomes independently of conduct problems. While there are differing, specific interventions for bullying behaviours and for conduct problems, it is unclear if such specific...

Background Peer victimization is associated with a wide range of mental health problems in youth, yet few studies described its association with mental health comorbidities. Methods To test the association between peer victimization timing and intensity and mental health comorbidities, we used data from 1216 participants drawn from the Quebec Long...

The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was...

Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Here, we report an advance on our original method (Belsky et al. 2020). We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 organ-system integrity indic...

Background Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood. Methods Individuals born in Swede...

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We...

Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PE...

Purpose: Growing evidence suggests that prospective informant-reports and retrospective self-reports of childhood maltreatment may be differentially associated with adult psychopathology. However, it remains unknown how associations for these two maltreatment reporting types compare when considering functional outcomes. The present study compared...

Objectives Personality traits are linked with healthy aging, but it is not clear how these associations come to manifest across the life-course and across generations. To study this question, we tested a series of hypotheses about (a) personality-trait prediction of markers of healthy aging across the life-course, (b) developmental origins, stabili...

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate...

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior ( N = 15,324 participants). In peripheral blood samples of 14,434 p...

Aims Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. This type of trauma is hypothesized to lead to more severe psychopathology and poorer cognitive function than other non-complex traumas, such as road traffic accidents. However, empirical testing of thi...

Background Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. These traumas are hypothesised to cause more severe psychopathology and poorer cognitive function than other non-complex traumas. However, empirical testing has been limited to clinical/convenienc...

In the face of the COVID-19 pandemic, the swift response of mental health research funders and institutions, service providers, and academics enabled progress toward understanding the mental health consequences. Nevertheless, there remains an urgent need to understand the true extent of the short- and long-term effects of the COVID-19 pandemic on m...

Importance: Air pollution exposure damages the brain, but its associations with the development of psychopathology are not fully characterized. Objective: To assess whether air pollution exposure in childhood and adolescence is associated with greater psychopathology at 18 years of age. Design, setting, and participants: The Environmental-Risk...

Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated DNAm variation is specific to an indiv...

The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes in adulthood are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methyla...

Knowledge about early risk factors for major depressive disorder (MDD) is critical to identify those who are at high risk. A multivariable model to predict adolescents’ individual risk of future MDD has recently been developed however its performance in a UK sample was far from perfect. Given the potential role of air pollution in the aetiology of...

Importance Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems. Objective To test the predictive accuracy of ACE screening for later health problems. Design, Setting, and...

Objective To understand whether genetic risk for attention-deficit hyperactivity disorder (ADHD) is associated with course of the disorder across childhood and into young adulthood. Method Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2,232 twins. ADHD was assessed at ages 5, 7,...

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational at...

The present study used quantitative and qualitative methods to explore how lonely young people are seen from others’ perspectives, in terms of their personality, behavior, and life circumstances. Data were drawn from the Environmental Risk Longitudinal Twin Study, a cohort of 2,232 individuals born in the U.K. in the mid-1990s. When participants we...

Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome...

The present study used a longitudinal and discordant twin design to explore in depth the developmental associations between victimization and loneliness from mid-childhood to young adulthood. The data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 individuals born in England and Wales during 1994–19...

Background: Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged e...

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We presen...

A recent Suicidal Drive Hypothesis posits that psychotic experiences (PEs) may serve to externalise internally generated and self-directed threat (i.e. self-injurious/suicidal behaviour (SIB)) in order to optimise survival, however, it must first be demonstrated that such internal threat can both precede and inform PEs. The current study conducted...

Being bullied can be an important contributing factor for the development of mental health problems in childhood and adolescence, and it is becoming clear that there are additional longer-term negative outcomes. Anti-bullying programs show promise in tackling bullying behaviors. However, the chances of eradicating bullying completely are minimal, a...

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 part...

Importance DNA methylation has been proposed as an epigenetic mechanism by which the childhood neighborhood environment may have implications for the genome that compromise adult health. Objective To ascertain whether childhood neighborhood socioeconomic disadvantage is associated with differences in DNA methylation by age 18 years. Design, Setti...

Background Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated variation is specific to an...

Background Associations of environmental exposures such as urban upbringing, deprivation and crime victimization with psychosis are well-established. An enduring question, however, is whether associations reflect a causal process. Emerging evidence using polygenic risk scores (PRS) suggests reverse causation, with adults at higher genetic risk for...

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is...

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is...

Objectives: To describe (1) the developmental trajectories of peer victimization from 6 to 17 years of age and (2) the early childhood behaviors and family characteristics associated with the trajectories. Methods: We used data from 1760 children enrolled in the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Par...

The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were i...

DNA methylation plays an important role in both normal human development and risk of disease. The most utilized method of assessing DNA methylation uses BeadChips, generating an epigenome-wide “snapshot” of >450,000 observations (probe measurements) per assay. However, the reliability of each of these measurements is not equal, and little considera...

Background A recent genome‐wide association study identified molecular‐genetic associations with age‐at‐first‐birth. However, the meaning of these genetic discoveries is unclear. Drawing on evidence linking early pregnancy with disinhibitory behavior, we tested the hypothesis that genetic discoveries for age‐at‐first‐birth predict disinhibition. M...

Background Attention deficit/hyperactivity disorder (ADHD) is associated with emotional problems, and their co‐occurrence often leads to worse outcomes. We investigated the developmental associations between ADHD and emotional problems from childhood to early adolescence and examined the genetic and environmental contributions to their developmenta...

Biological aging is the gradual and progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the rate of biological aging are needed to serve as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging to extend healthspan. We re...

Importance Key outcomes for persons with psychiatric disorders include subjection to violence and perpetration of violence. The occurrence of these outcomes and their associations with psychiatric disorders need to be clarified. Objective To estimate the associations of a wide range of psychiatric disorders with the risks of subjection to violence...

Educational attainment (EA) is influenced by cognitive abilities and by other characteristics and traits. However little is known about the genetic architecture of these "non-cognitive" contributions to EA. Here, we use Genomic Structural Equation Modelling and results of prior genome-wide association studies (GWASs) of EA (N = 1,131,881) and cogni...

Objective: Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variab...

Significance Despite growing up in the same family, siblings do not always see their family’s social standing identically. Eighteen-year-old twins who rated their family as having higher social standing, compared with their cotwin’s rating, had fewer difficulties negotiating the transition to adulthood: they were less likely to be convicted of a cr...

What impact does formal punishment have on antisocial conduct—does it deter or promote it? The findings from a long line of research on the labeling tradition indicate formal punishments have the opposite‐of‐intended consequence of promoting future misbehavior. In another body of work, the results show support for deterrence‐based hypotheses that p...

Background Attention-deficit hyperactivity disorder (ADHD) is associated with poorer cognitive functioning. We used a developmental, genetically-sensitive approach to examine intelligence quotient (IQ) from early childhood to young adulthood among those with different ADHD courses to investigate whether changes in ADHD were reflected in differences...

Background: Victimized children are at greater risk for psychopathology than non-victimized peers. However, not all victimized children develop psychiatric disorders, and accurately identifying which victimized children are at greatest risk for psychopathology is important to provide targeted interventions. This study sought to develop and internal...

Importance Childhood stress exposure is associated with inflammation as measured by C-reactive protein (CRP) and interleukin 6 (IL-6). However, findings are inconsistent and effect sizes are small. The addition of soluble urokinase plasminogen activator receptor (suPAR), a new biomarker of chronic inflammation, may improve measurement of stress-rel...

This study tested implications of new genetic discoveries for understanding the association between parental investment and children’s educational attainment. A novel design matched genetic data from 860 British mothers and their children with home‐visit measures of parenting: the E‐Risk Study. Three findings emerged. First, both mothers’ and child...

Background: Childhood victimization elevates the average risk of developing functional impairment in adulthood. However, not all victimized children demonstrate poor outcomes. Although research has described factors that confer vulnerability or resilience, it is unknown if this knowledge can be translated to accurately identify the most vulnerable...

Background: Childhood victimization elevates the average risk of developing functional impairment in adulthood. However, not all victimized children demonstrate poor outcomes. Although research has described factors that confer vulnerability or resilience, it is unknown if this knowledge can be translated to accurately identify the most vulnerable...