Publications by authors named "Edward D Barker"

98 Publications

Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis.

Am J Med Genet B Neuropsychiatr Genet 2021 Jun 25;186(4):228-241. Epub 2021 Jun 25.

Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Low prosocial behavior in childhood has been consistently linked to later psychopathology, with evidence supporting the influence of both genetic and environmental factors on its development. Although neonatal DNA methylation (DNAm) has been found to prospectively associate with a range of psychological traits in childhood, its potential role in prosocial development has yet to be investigated. This study investigated prospective associations between cord blood DNAm at birth and low prosocial behavior within and across four longitudinal birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. We examined (a) developmental trajectories of "chronic-low" versus "typical" prosocial behavior across childhood in a case-control design (N = 2,095), and (b) continuous "low prosocial" scores at comparable cross-cohort time-points (N = 2,121). Meta-analyses were performed to examine differentially methylated positions and regions. At the cohort-specific level, three CpGs were found to associate with chronic low prosocial behavior; however, none of these associations was replicated in another cohort. Meta-analysis revealed no epigenome-wide significant CpGs or regions. Overall, we found no evidence for associations between DNAm patterns at birth and low prosocial behavior across childhood. Findings highlight the importance of employing multi-cohort approaches to replicate epigenetic associations and reduce the risk of false positive discoveries.
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http://dx.doi.org/10.1002/ajmg.b.32862DOI Listing
June 2021

Genome-wide DNA methylation patterns associated with general psychopathology in children.

J Psychiatr Res 2021 Aug 28;140:214-220. Epub 2021 May 28.

Department of Child and Adolescent Psychiatry/ Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.

Psychiatric symptoms are interrelated and found to be largely captured by a general psychopathology factor (GPF). Although epigenetic mechanisms, such as DNA methylation (DNAm), have been linked to individual psychiatric outcomes, associations with GPF remain unclear. Using data from 440 children aged 10 years participating in the Generation R Study, we examined the associations of DNAm with both general and specific (internalizing, externalizing) factors of psychopathology. Genome-wide DNAm levels, measured in peripheral blood using the Illumina 450K array, were clustered into wider co-methylation networks ('modules') using a weighted gene co-expression network analysis. One co-methylated module associated with GPF after multiple testing correction, while none associated with the specific factors. This module comprised of 218 CpG probes, of which 198 mapped onto different genes. The CpG most strongly driving the association with GPF was annotated to FZD1, a gene that has been implicated in schizophrenia and wider neurological processes. Associations between the probes contained in the co-methylated module and GPF were supported in an independent sample of children from the Avon Longitudinal Study of Parents and Children (ALSPAC), as evidenced by significant correlations in effect sizes. These findings might contribute to improving our understanding of dynamic molecular processes underlying complex psychiatric phenotypes.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.029DOI Listing
August 2021

Childcare Attendance and Academic Achievement at Age 16 Years.

JAMA Pediatr 2021 Jun 7. Epub 2021 Jun 7.

School of Public Health, University of Montreal, Montreal, Quebec, Canada.

Importance: Low school preparedness is linked to high school dropout, poor employment, and negative outcomes. Childcare attendance may increase school readiness and foster academic achievement.

Objective: To explore whether childcare attendance was associated with academic achievement at the end of compulsory schooling (age 16 years in the UK), whether maternal education level was a moderator, and the benefit-cost ratio of childcare regarding productivity returns of academic achievement.

Design, Setting, And Participants: In this cohort study, data were included from the Avon Longitudinal Study of Parents and Children (ALSPAC) born from April 1991 to December 1992 and the UK National Pupil Database for examination results. Data on academic achievement at age 16 years were available for 11 843 participants. Data were collected from June 2006 to June 2008, and data were analyzed from September 2019 to May 2020.

Exposures: On average, 3.7%, 5.9%, and 90.4% attended childcare full time, part time, and less than 10 hours per week, respectively. Maternal education was assessed by questionnaire during pregnancy. Analyses included weights for population representativeness and propensity score weights to account for parental selection into childcare.

Main Outcomes And Measures: Academic achievement was defined as no certificate, Level 1 General Certificate of Secondary Education (GCSE; limited training), or Level 2 GCSE (qualification for academic post-16 education; high school diploma equivalent). Lifetime productivity return estimates were withdrawn from previous economic analysis based on pupil's qualifications.

Results: Of 14 541 children in the ALSPAC study, 8936 children had complete data on childcare attendance, academic achievement, and maternal education levels. Of these, 4499 (50.3%) were male. Attending childcare was associated with higher probabilities of obtaining a Level 1 or 2 GCSE qualification (Level 1: relative risk, 1.41; 95% CI, 1.16-1.73; Level 2: relative risk, 1.62; 95% CI, 1.30-2.01); however, this association was moderated by the child's maternal education level. When children of mothers with low education attended childcare, their probability of no GCSE qualification went from 28.9% (95% CI, 26.8-31.0) to 20.3% (95% CI, 18.0-22.8), whereas children of mothers with higher education had a probability of no qualification of less than 10% regardless of childcare attendance. The benefit-cost ratio for each £1 (US $1.40) invested in full-time childcare attendance for children of mothers with low education was £1.71 (95% CI, 1.03-2.45; US $2.39; 95% CI, 1.44-3.43) for those who reached a Level 2 GCSE qualification.

Conclusions And Relevance: Promoting universal childcare with facilitated access for children of lower socioeconomic backgrounds deserves to be considered as a way to reduce the intergenerational transmission of low academic achievement.
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http://dx.doi.org/10.1001/jamapediatrics.2021.1192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185627PMC
June 2021

Etiological pathways of depressive and anxiety symptoms linked to personality traits: A genetically-informative longitudinal study.

J Affect Disord 2021 08 15;291:261-269. Epub 2021 May 15.

Faculty of Letters, Keio University, Japan.

Background: The comorbidity of depression and anxiety is associated with an increased risk of prolonged adverse mental health status. However, little is currently known about their genetic and environmental influences that help to explain both the comorbidity and distinctiveness. Using longitudinal twin data, the present study investigated both the overlapping and distinct relationships between depression and anxiety viewed from the perspective of Gray's Reinforcement Sensitivity Theory (RST): two personality traits of the Behavioral Inhibition and Activation Systems (BIS and BAS).

Methods: A total of 422 twin pairs (298 monozygotic and 124 dizygotic pairs) participated by completing a personality questionnaire at wave 1, and mood symptoms questionnaires at wave 2. The waves were on average 2.23 years apart.

Results: Multivariate Cholesky decomposition indicated that the genetic variance of the personality traits (BIS and BAS) explained all of the genetic variance in depressive and anxiety symptoms. Additionally, genetic factors related to the BIS positively explained depressive and anxiety symptoms, whereas genetic factors related to the BAS negatively explained only depressive symptoms.

Limitations: Limitations include shorter time interval and the reliance on self-reported data.

Conclusions: The present study provided evidence explaining the overlap and differentiation of depressive and anxiety symptoms by using data on personality traits in a longitudinal, genetically-informative design. The findings suggested the personality traits from Gray's RST model played an important role in the prediction, and clarified the description, of both depressive and anxiety symptoms.
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http://dx.doi.org/10.1016/j.jad.2021.05.004DOI Listing
August 2021

Sex differences in neural correlates of common psychopathological symptoms in early adolescence.

Psychol Med 2021 Mar 26:1-11. Epub 2021 Mar 26.

Centre for Population Neuroscience and Stratified Medicine (PONS) and Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

Background: Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.

Methods: Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).

Results: We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = -0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = -0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = -0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = -0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.

Conclusions: Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
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http://dx.doi.org/10.1017/S0033291720005140DOI Listing
March 2021

Epigenetic profiling of social communication trajectories and co-occurring mental health problems: a prospective, methylome-wide association study.

Dev Psychopathol 2021 Jan 26:1-10. Epub 2021 Jan 26.

Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

While previous studies suggest that both genetic and environmental factors play an important role in the development of autism-related traits, little is known about potential biological mechanisms underlying these associations. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined prospective associations between DNA methylation (DNAm: nbirth = 804, nage 7 = 877) and trajectories of social communication deficits at age 8-17 years. Methylomic variation at three loci across the genome (false discovery rate = 0.048) differentiated children following high (n = 80) versus low (n = 724) trajectories of social communication deficits. This differential DNAm was specific to the neonatal period and not observed at 7 years of age. Associations between DNAm and trajectory membership remained robust after controlling for co-occurring mental health problems (i.e., hyperactivity/inattention, conduct problems). The three loci identified at birth were not replicated in the Generation R Study. However, to the best of our knowledge, ALSPAC is the only study to date that is prospective enough to examine DNAm in relation to longitudinal trajectories of social communication deficits from childhood to adolescence. Although the present findings might point to potentially novel sites that differentiate between a high versus low trajectory of social communication deficits, the results should be considered tentative until further replicated.
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http://dx.doi.org/10.1017/S0954579420001662DOI Listing
January 2021

Exposure to Bullying and General Psychopathology: A Prospective, Longitudinal Study.

Res Child Adolesc Psychopathol 2021 06 22;49(6):727-736. Epub 2021 Jan 22.

Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Although there is mounting evidence that the experience of being bullied associates with both internalizing and externalizing symptoms, it is not known yet whether the identified associations are specific to these symptoms, or shared between them. The primary focus of this study is to assess the prospective associations of bullying exposure with both general and specific (i.e., internalizing, externalizing) factors of psychopathology. This study included data from 6,210 children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Child bullying was measured by self-report at ages 8 and 10 years. Child psychopathology symptoms were assessed by parent-interview, using the Development and Well-being Assessment (DAWBA) at ages 7 and 13 years. Bullying exposure significantly associated with the general psychopathology factor in early adolescence. In particular, chronically victimized youth exposed to multiple forms of bullying (i.e., both overt and relational) showed higher levels of general psychopathology. Bullying exposure also associated with both internalizing and externalizing factors from the correlated-factors model. However, the effect estimates for these factors decreased considerably in size and dropped to insignificant for the internalizing factor after extracting the shared variance that belongs to the general factor of psychopathology. Using an integrative longitudinal model, we found that higher levels of general psychopathology at age 7 also associated with bullying exposure at age 8 which, in turn, associated with general psychopathology at age 13 through its two-year continuity. Findings suggest that exposure to bullying is a risk factor for a more general vulnerability to psychopathology.
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http://dx.doi.org/10.1007/s10802-020-00760-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096758PMC
June 2021

Association of Genetic and Phenotypic Assessments With Onset of Disordered Eating Behaviors and Comorbid Mental Health Problems Among Adolescents.

JAMA Netw Open 2020 12 1;3(12):e2026874. Epub 2020 Dec 1.

Technische Universität Dresden, Faculty of Medicine Carl Gustav Carus, Department of Psychiatry and Psychotherapy, Section of Systems Neuroscience, Dresden, Germany.

Importance: Eating disorders are serious mental disorders with increasing prevalence. Without early identification and treatment, eating disorders may run a long-term course.

Objective: To characterize any associations among disordered eating behaviors (DEBs) and other mental health disorders and to identify early associations with the development of symptoms over time.

Design, Setting, And Participants: This multicenter, population-based, longitudinal cohort study used data from baseline (collected in 2010), follow-up 1 (collected in 2012), and follow-up 2 (collected in 2015) of the IMAGEN Study, which included adolescents recruited from 8 European sites. The present study assessed data from 1623 healthy adolescents, aged 14 years at baseline, recruited from high schools. Data analyses were performed from January 2018 to September 2019.

Main Outcomes And Measures: Body mass index (BMI), mental health symptoms, substance use behaviors, and personality variables were investigated as time-varying associations of DEBs (dieting, binge eating, and purging) or change in BMI over time. Polygenic risk scores were calculated to investigate genetic contributions associated with BMI, attention-deficit/hyperactivity disorder (ADHD) and neuroticism to DEBs.

Results: In this cohort study of 1623 adolescents (829 girls [51.1%]) recruited at a mean (SD) age of 14.5 (0.4) years and followed up at ages 16 and 19 years, 278 adolescents (17.1%) reported binge eating, 334 adolescents (20.6%) reported purging, and 356 adolescents (21.9%) reported dieting at 14, 16, or 19 years. Among the precursors of DEBs, high BMI was associated with future dieting (OR, 3.44; 95% CI, 2.09-5.65). High levels of neuroticism (OR, 1.04; 95% CI, 1.01-1.06), conduct problems (OR, 1.41; 95% CI, 1.17-1.69), and deliberate self-harm (OR, 2.18; 95% CI, 1.37-3.45) were associated with future binge eating. Low agreeableness (OR, 0.95; 95% CI, 0.92-0.97), deliberate self-harm (OR, 2.59; 95% CI, 1.69-3.95), conduct problems (OR, 1.42; 95% CI, 1.20-1.68), alcohol misuse (OR, 1.31; 95% CI, 1.10-1.54), and drug abuse (OR, 2.91; 95% CI, 1.78-4.74) were associated with future purging. Polygenetic risk scores for BMI were associated with dieting (at 14 years: OR, 1.27; lower bound 95% CI, 1.08; at 16 years: OR, 1.38; lower bound 95% CI, 1.17); ADHD, with purging (at 16 years: OR, 1.25; lower bound 95% CI, 1.08; at 19 years, OR, 1.23; lower bound 95% CI, 1.06); and neuroticism, with binge eating (at 14 years: OR, 1.32; lower bound 95% CI, 1.11; at 16 years: OR, 1.24; lower bound 95% CI, 1.06), highlighting distinct etiologic overlaps between these traits. The DEBs predated other mental health problems, with dieting at 14 years associated with future symptoms of depression (OR, 2.53; 95% CI, 1.56-4.10), generalized anxiety (OR, 2.27; 95% CI, 1.14-4.51), deliberate self-harm (OR, 2.10; 95% CI, 1.51-4.24), emotional problems (OR, 1.24; 95% CI, 1.08-1.43), and smoking (OR, 2.16; 95% CI, 1.36-3.48). Purging at 14 years was also associated with future depression (OR, 2.87; 95% CI, 1.69-5.01) and anxiety (OR, 2.48; 95% CI, 1.49-4.12) symptoms.

Conclusions And Relevance: The findings of this study delineate temporal associations and shared etiologies among DEBs and other mental health disorders and emphasize the potential of genetic and phenotypical assessments of obesity, behavioral disorders, and neuroticism to improve early and differential diagnosis of eating disorders.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.26874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711322PMC
December 2020

Are there causal relationships between attention-deficit/hyperactivity disorder and body mass index? Evidence from multiple genetically informed designs.

Int J Epidemiol 2021 05;50(2):496-509

Department of Clinical, Educational and Health Psychology, University College London, London, UK.

Background: Attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI) are associated. However, it remains unclear whether this association reflects causal relationships in either direction or confounding. Here, we implemented genetically informed methods to examine bidirectional causality and potential confounding.

Methods: Three genetically informed methods were employed: (i) cross-lagged twin-differences analyses to assess bidirectional effects of ADHD symptoms and BMI at ages 8, 12, 14 and 16 years in 2386 pairs of monozygotic twins from the Twins Early Development Study (TEDS); (ii) within- and between-family ADHD and BMI polygenic score (PS) analyses in 3320 pairs of dizygotic TEDS twins; and (iii) two-sample bidirectional Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) on ADHD (N = 55,374) and BMI (N = 806,834).

Results: Mixed results were obtained across the three methods. Twin-difference analyses provided little support for cross-lagged associations between ADHD symptoms and BMI over time. PS analyses were consistent with bidirectional relationships between ADHD and BMI, with plausible time-varying effects from childhood to adolescence. MR findings also suggested bidirectional causal effects between ADHD and BMI. Multivariable MR indicated the presence of substantial confounding in bidirectional relationships.

Conclusions: The three methods converged to highlight multiple sources of confounding in the association between ADHD and BMI. PS and MR analyses suggested plausible causal relationships in both directions. Possible explanations for mixed causal findings across methods are discussed.
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http://dx.doi.org/10.1093/ije/dyaa214DOI Listing
May 2021

Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis.

Transl Psychiatry 2020 11 12;10(1):398. Epub 2020 Nov 12.

Clinical Child & Family Studies, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.
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http://dx.doi.org/10.1038/s41398-020-01058-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665047PMC
November 2020

Promoting better functioning among children exposed to high levels of family adversity: the protective role of childcare attendance.

J Child Psychol Psychiatry 2021 Jun 21;62(6):762-770. Epub 2020 Aug 21.

Department of Psychology, King's College London, London, UK.

Background: Children exposed to early adversity are vulnerable to cognitive impairments and externalizing behaviors. Attending childcare may, however, partly buffer this detrimental effect by providing social and cognitive stimulation in a secure environment. The aims of this study were (a) to determine whether the association between exposure to adversity and later externalizing behaviors is mediated by children's cognitive abilities, and (b) to examine if childcare attendance moderates this mediation-thereby highlighting a protective function of children's childcare attendance.

Methods: Data come from the Avon Longitudinal Study of Children and Parents (N = 6,149). Exposure to adversity was assessed by maternal reports three times from the second trimester of the mother's pregnancy to the child's fourth year of age. Childcare attendance was assessed on four occasions between eight months and three years of age. Factors explaining differences in childcare attendance were controlled using propensity score weights. Children's cognitive abilities were assessed by the Weschler Intelligence Scale for Children at eight years of age, and externalizing behaviors were reported by mothers using the Development and Well-Being Assessment interview at 10, 13, and 15 years of age.

Results: Notably, lower cognitive abilities partly accounted for the higher levels of externalizing behaviors in adolescents exposed to adversity (B indirect effect = 0.02, 95% CI = 0.007-0.03, p < .01). Importantly, childcare attendance moderated this indirect effect. For children exposed to adversity, being in maternal care was associated with lower cognitive abilities which were related to higher levels of externalizing behaviors. On the contrary, for children exposed to adversity, attending childcare was associated with higher cognitive abilities which were linked to lower levels of externalizing behaviors.

Conclusions: Easily accessible community childcare may be a relatively low-cost public health strategy to prevent the emergence of externalizing behavioral problems in adolescence through its positive effects on cognitive abilities.
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http://dx.doi.org/10.1111/jcpp.13313DOI Listing
June 2021

Development of Disordered Eating Behaviors and Comorbid Depressive Symptoms in Adolescence: Neural and Psychopathological Predictors.

Biol Psychiatry 2020 Jun 10. Epub 2020 Jun 10.

Department of Psychiatry and Neuroimaging Center, Technische Universitat Dresden, Dresden, Germany.

Background: Eating disorders are common in adolescence and are devastating and strongly comorbid with other psychiatric disorders. Yet little is known about their etiology, knowing which would aid in developing effective preventive measures.

Methods: Longitudinal assessments of disordered eating behaviors (DEBs)-binge-eating, purging, and dieting-and comorbid psychopathology were measured in 1386 adolescents from the IMAGEN study. Development of DEBs and associated mental health problems was investigated by comparing participants who reported symptoms at ages 16 or 19 years, but not at age 14 years, with asymptomatic control participants. Voxel-based morphometry and psychopathological differences at age 14 were investigated to identify risk factors for the development of DEBs and associated mental health problems.

Results: DEBs and depressive symptoms developed together. Emotional and behavioral problems, including symptoms of attention-deficit/hyperactivity disorder and conduct disorder, predated their development. Alterations in frontostriatal brain areas also predated the development of DEBs and depressive symptoms. Specifically, development of binge-eating was predicted by higher gray matter volumes in the right putamen/globus pallidus at age 14. Conversely, development of purging and depressive symptoms was predicted by lower volumes in the medial orbitofrontal, dorsomedial, and dorsolateral prefrontal cortices. Lower gray matter volumes in the orbitofrontal and anterior cingulate cortices mediated the relationship between attention-deficit/hyperactivity disorder and conduct disorder symptoms and future purging and depressive symptoms.

Conclusions: These findings suggest that alterations in frontal brain circuits are part of the shared etiology among eating disorders, attention-deficit/hyperactivity disorder, conduct disorder, and depression and highlight the importance of a transdiagnostic approach to treating these conditions.
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http://dx.doi.org/10.1016/j.biopsych.2020.06.003DOI Listing
June 2020

Why does early childhood deprivation increase the risk for depression and anxiety in adulthood? A developmental cascade model.

J Child Psychol Psychiatry 2020 09 6;61(9):1043-1053. Epub 2020 Feb 6.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Background: Using data from the English & Romanian Adoptees (ERA) study, we recently reported that early time-limited exposure to severe institutional deprivation is associated with early-onset and persistent neurodevelopmental problems and later-onset emotional problems. Here, we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress.

Methods: The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity, exposure to adverse life events, and functioning in work and interpersonal relationships.

Results: The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity, and emotional problems were inconclusive.

Conclusions: Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model.
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http://dx.doi.org/10.1111/jcpp.13205DOI Listing
September 2020

Erotic Target Identity Inversions Among Men and Women in an Internet Sample.

J Sex Med 2020 01 5;17(1):99-110. Epub 2019 Dec 5.

Psychology Department, Institute of Psychiatry, Psychology, and Neuroscience, King's College London. Electronic address:

Introduction: Erotic target identity inversions (ETIIs) are poorly studied paraphilias that involve sexual arousal by the idea or fantasy of being the object of one's sexual desires.

Aim: To conduct a large non-clinical online survey to investigate self-reported sexual arousal, behavioral expression, and psychological correlates of 4 proposed ETIIs.

Methods: A total of 736 natal males and 549 natal females responded to items about self-reported sexual arousal to the idea of acting as an animal (autoanthropomorphozoophilia) or the idea of acting as a child or infant (autonepiophilia), natal males reporting arousal to the idea of acting as a woman (autogynephilia), and natal females reporting arousal to the idea of acting as a man (autoandrophilia). Data pertaining to sexual orientation, childhood gender nonconformity, gender identity discomfort, autism, masochism, and humiliation were also collected.

Main Outcome Measures: The main outcome was a measure of self-reported arousal and expression of the ETIIs being explored using 4 items: arousal level (-3 to 3) when imagining being the erotic target exemplar; frequency of engagement in dressing or behaving like their preferred target (0-4); strength of feeling that they would be better off as the target (0-4); and the frequency of consideration of making physical changes to look or function more like the target (0-4).

Results: Mild levels of reported sexual arousal to the idea of being the preferred erotic target were common among the 4 groups, characterizing about half of them. Gender identity discomfort was associated with autogynephilia, autoandrophilia, and autoanthropomorphozoophilia. Greater gender nonconformity was associated with autogynephilia, autoandrophilia, and autonepiophilia. Autism scores were associated with autoandrophilia and autonepiophilia. Masochism was not associated with ETII scores, but humiliation was.

Clinical Implications: Findings suggest that it may be important to distinguish between subgroups of those with different levels and types of ETII arousal/expression.

Strengths & Limitations: Strengths of this study include the large, non-clinical sample of men and women for the investigation of ETIIs and the inclusion of measures of psychological correlates. The use of an Internet sample with self-report measures may be unrepresentative, although the Internet has the advantage of allowing recruitment from stigmatized or unusual groups. The cross-sectional nature limits our conclusions, as no causal inferences can be made.

Conclusion: The results support the concept of ETIIs as a paraphilic dimension in non-clinical samples and the possible role of gender-related psychological factors. Brown A, Barker ED, Rahman Q. Erotic Target Identity Inversions Among Men and Women in an Internet Sample. J Sex Med 2020;17:99-110.
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http://dx.doi.org/10.1016/j.jsxm.2019.10.018DOI Listing
January 2020

Assessing the content specificity of interpretation biases in community adolescents with persistent and interfering pain.

Pain 2020 02;161(2):319-327

Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

The tendency to select threatening over benign interpretations of ambiguous bodily sensations and cues characterises young people with chronic pain. However, previous studies disagree over whether these biases extend to nonbodily harm situations such as social evaluation. Understanding the content of these biases is crucial to the development of pain management strategies seeking to modify such biases. Two hundred forty-three young people aged 16 to 19 years completed an expanded version of the Adolescent Interpretation of Bodily Threat task. Using a factor-analytic approach, we removed items that did not consistently associate with bodily harm or social evaluation. Next, we examined whether the variance underlying negative and benign interpretations of bodily harm and social evaluation situations were best represented as a common factor (ie, one-factor model), 2 distinct factors (ie, 2-factor model), or one common and 2 distinct factors (ie, 2-factor bifactor model) in all adolescents. We then compared youth with and without persistent and impairing pain on factor scores derived from the best-fitting model. Although negative interpretations of bodily harm and social evaluation situations emerged as distinct factors, benign interpretations across situations were best captured by a common factor and 2 situation-specific factors (ie, bifactor model). Group comparisons showed that young people with moderate-to-high pain interference were more likely to endorse negative interpretations across all situations, and less likely to manifest a general benign interpretational style, than youth without interfering pain, although some of these group differences were explained by co-occurring anxiety and depressive symptoms. Replication of these findings is needed.
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http://dx.doi.org/10.1097/j.pain.0000000000001723DOI Listing
February 2020

Serum cholesterol, MTHFR methylation, and symptoms of depression in children.

Dev Psychol 2019 Dec 17;55(12):2575-2586. Epub 2019 Oct 17.

Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience.

Depression is associated with dietary factors and epigenetics. Serum cholesterol, which is prone to dietary influences, has been linked to symptoms of depression. This relationship may be (in part) due to altered epigenetic regulation of Methylenetetrahydrofolate Reductase (MTHFR). MTHFR codes for the MTHFR enzyme, which has diverse metabolic functions, and has recently been linked individually with diet, serum cholesterol levels and depressive symptoms. In 514 mother-child pairs, we examined prospective relationships between maternal (pregnancy) and child (7 years) serum cholesterol, MTHFR DNA methylation (DNAm; birth, 7 years), and development of depression symptoms from 8-15 years. After adjusting for potential confounding, we had three main findings. First, higher prenatal cholesterol associated (at a small effect size) with higher MTHFR DNAm at birth. Second, there was small effect size continuity for MTHFR DNAm between birth and age 7. Third, higher age 7 MTHFR DNAm associated with higher initial symptoms of depression symptoms at age 8, again at a small effect size. Overall, our findings provide preliminary evidence for a relationship between prenatal cholesterol, MTHFR DNAm, and symptoms of depression in children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/dev0000831DOI Listing
December 2019

A Systematic Scoping Review of the Prevalence, Etiological, Psychological, and Interpersonal Factors Associated with BDSM.

J Sex Res 2020 07 16;57(6):781-811. Epub 2019 Oct 16.

Psychology Department, Institute of Psychiatry, Psychology, and Neuroscience, King's College London.

BDSM (bondage, discipline, dominance, submission, and sadomasochism) encompasses a diverse set of sexual interests. Research interests in BDSM have been historically underpinned by examining potential mental health issues, unhealthy fixations on specific sexual behaviors, and/or the presence of childhood trauma, as is predicted by psychopathological and psychoanalytic models. The objective of this scoping review was to provide an overview of the current landscape of BDSM research, including incidence rates, evidence for psychopathological, psychoanalytical, biological, and social etiological factors, demographics of BDSM practitioners, and the psychological correlates of those with BDSM interests. After the literature search and screening process, 60 articles were included. BDSM related fantasies were found to be common (40-70%) in both males and females, while about 20% reported engaging in BDSM. Results show little support for psychopathologic or psychoanalytic models. In the selected samples studied, BDSM practitioners appear to be white, well educated, young, and do not show higher rates of mental health or relationship problems. Research supports BDSM being used as a broadening of sexual interests and behaviors instead of a fixation on a specific interest. Future empirical research should focus on non-pathological models of BDSM, discrimination of BDSM practitioners, interpersonal relationships, and biological factors.
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http://dx.doi.org/10.1080/00224499.2019.1665619DOI Listing
July 2020

Identification of neurobehavioural symptom groups based on shared brain mechanisms.

Nat Hum Behav 2019 12 7;3(12):1306-1318. Epub 2019 Oct 7.

NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.

Most psychopathological disorders develop in adolescence. The biological basis for this development is poorly understood. To enhance diagnostic characterization and develop improved targeted interventions, it is critical to identify behavioural symptom groups that share neural substrates. We ran analyses to find relationships between behavioural symptoms and neuroimaging measures of brain structure and function in adolescence. We found two symptom groups, consisting of anxiety/depression and executive dysfunction symptoms, respectively, that correlated with distinct sets of brain regions and inter-regional connections, measured by structural and functional neuroimaging modalities. We found that the neural correlates of these symptom groups were present before behavioural symptoms had developed. These neural correlates showed case-control differences in corresponding psychiatric disorders, depression and attention deficit hyperactivity disorder in independent clinical samples. By characterizing behavioural symptom groups based on shared neural mechanisms, our results provide a framework for developing a classification system for psychiatric illness that is based on quantitative neurobehavioural measures.
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http://dx.doi.org/10.1038/s41562-019-0738-8DOI Listing
December 2019

Long-term cognitive outcomes in tuberous sclerosis complex.

Dev Med Child Neurol 2020 03 19;62(3):322-329. Epub 2019 Sep 19.

Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Aim: To investigate the interdependence between risk factors associated with long-term intellectual development in individuals with tuberous sclerosis complex (TSC).

Method: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with TSC. In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with TSC and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to IQ at phase 2.

Results: Intellectual disability was present in 57% of individuals with TSC. Individuals without intellectual disability had significantly lower mean IQ compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with TSC who had a slower gain in IQ from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to IQ in middle childhood and adolescence.

Interpretation: Early-onset and severe epilepsy in the first 2 years of life are associated with increased risk of long-term intellectual disability in individuals with TSC, emphasizing the importance of early and effective treatment or prevention of epilepsy.

What This Paper Adds: Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC). Those with TSC without intellectual disability had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC.
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http://dx.doi.org/10.1111/dmcn.14356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027810PMC
March 2020

Health and Functional Outcomes for Shared and Unique Variances of Interpersonal Callousness and Low Prosocial Behavior.

J Psychopathol Behav Assess 2019 Aug 15;41(3):353-365. Epub 2019 Sep 15.

Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK.

Previous factor-analytic studies identify significant comorbidity between interpersonal-callous (IC) traits and low prosocial behavior (LPB), which, in turn, is associated with high levels of childhood risk exposure and psychopathology. Longitudinal associations between IC, LPB, or their combination, and early-adult health and social functioning have not been investigated, however. Extending a previously-identified bifactor model within a prospective birth cohort, this study applied latent path analysis to test direct and indirect pathways (via adolescent delinquency, substance use, and physical activity) between these general and specific factors (age 13) and (i) emotional problems (age 18), (ii) physical health problems (age 18), and (iii) classification as 'not in education, employment, or training' (NEET; age 20). All models controlled for childhood adversity and IQ. Bifactor-specific estimates indicated that the residual IC factor did not reliably denote unique variance over and above a general factor (IC/LPB). IC/LPB itself was directly associated with NEET classification, while the residual LPB factor was associated with emotional and physical health. IC/LPB also indirectly associated with emotional problems via greater adolescent delinquency, and with physical health problems via lower physical activity. In contrast, residual LPB variance was either non-significantly or negatively related to these adolescent domains. Findings indicate that the shared variance underlying IC and LPB confers an increased risk for poor health and functional outcomes in emerging adulthood, and highlight delinquency and physical inactivity as potential adolescent treatment targets that may mitigate the risk for health difficulties at high levels of this IC/LPB construct.
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http://dx.doi.org/10.1007/s10862-019-09756-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116552PMC
August 2019

Pediatric traumatic brain injury and antisocial behavior: are they linked? A systematic review.

Brain Inj 2019 21;33(10):1272-1292. Epub 2019 Jul 21.

a King's College London, Institute of Psychology, Psychiatry, and Neuroscience, Department of Psychology , London , UK.

: Despite growing evidence supporting a link between pediatric traumatic brain injury (TBI) and antisocial behavior, little work has rigorously evaluated this. This review aimed to explore systematically previous literature on the association between TBI before the age of 19 and severe behavioral problems such as violence, aggression and assault. : All articles published from 1990 to 2018 were searched using four major databases, alongside manual searching and cross-referencing. : Sixteen articles met the eligibility criteria. Overall, they supported an association between pediatric TBI and antisocial behavior. Factors were identified that might influence this link, such as, for example, TBI severity and substance use. : The review identified several issues in the current literature, highlighting key areas for improvement. It is imperative that more attention is paid to gathering detailed information regarding the temporal sequencing of events and TBI severity; evaluating the contribution of biopsychosocial variables co-occurring with TBI and antisocial behavior; disentangling which outcomes are specific to TBI versus any injury. The review has implications for the health and justice systems; regardless of whether TBI is the cause versus a contributing factor to antisocial behavior, increased awareness of their association could lead to more comprehensive assessments, tailored interventions and effective sentencing.
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http://dx.doi.org/10.1080/02699052.2019.1641621DOI Listing
July 2020

Do ADHD-impulsivity and BMI have shared polygenic and neural correlates?

Mol Psychiatry 2021 03 21;26(3):1019-1028. Epub 2019 Jun 21.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.
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http://dx.doi.org/10.1038/s41380-019-0444-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910212PMC
March 2021

The Influence of Treatment Engagement on Positive Outcomes in the Context of a School-Based Intervention for Students with Externalizing Behavior Problems.

J Abnorm Child Psychol 2019 09;47(9):1437-1454

Department of Psychology, The University of Alabama, Tuscaloosa, AL, USA.

We examined the stability of and cross-influences between externalizing behaviors and intervention engagement among children participating in a randomized clinical trial of an intervention for disruptive behavioral youth. Analyses also accounted for the influence of caregiver depression, family relationship quality, and sociodemographic factors (race, income) on the relationship between behaviors and intervention engagement. Analyses were based on 118 children participating in the Coping Power intervention. Composite variables were created to represent externalizing behaviors and intervention engagement constructs. Associations between these composite variables were examined over 24 treatment sessions. Findings indicated a regressive relationship among externalizing behaviors, i.e., baseline externalizing behaviors were positively associated with immediate follow-up behaviors. There were also dynamic relationships observed among engagement constructs. Notably, engagement with in-session activities during sessions 1-8 was positively associated with out-of-session activity engagement during the same treatment time period. Engagement with out-of-session activities during sessions 1-8 was positively associated with in-session activity engagement during sessions 9-16, indicating a complete mediation between early and middle in-session engagement through the mechanism of early out-of-session engagement. A crosslag relationship was observed: middle in-session engagement was negatively associated with externalizing behaviors at immediate follow-up. Finally, an interaction of race by income on immediate follow-up externalizing behaviors was observed, such that Black children's externalizing behaviors remain static regardless of income level while White children's behaviors decreased with higher income. Our findings support the contention that focusing on intervention engagement may be especially important in prevention interventions.
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http://dx.doi.org/10.1007/s10802-019-00525-6DOI Listing
September 2019

Peer victimization and its impact on adolescent brain development and psychopathology.

Mol Psychiatry 2020 11 12;25(11):3066-3076. Epub 2018 Dec 12.

Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Chronic peer victimization has long-term impacts on mental health; however, the biological mediators of this adverse relationship are unknown. We sought to determine whether adolescent brain development is involved in mediating the effect of peer victimization on psychopathology. We included participants (n = 682) from the longitudinal IMAGEN study with both peer victimization and neuroimaging data. Latent profile analysis identified groups of adolescents with different experiential patterns of victimization. We then associated the victimization trajectories and brain volume changes with depression, generalized anxiety, and hyperactivity symptoms at age 19. Repeated measures ANOVA revealed time-by-victimization interactions on left putamen volume (F = 4.38, p = 0.037). Changes in left putamen volume were negatively associated with generalized anxiety (t = -2.32, p = 0.020). Notably, peer victimization was indirectly associated with generalized anxiety via decreases in putamen volume (95% CI = 0.004-0.109). This was also true for the left caudate (95% CI = 0.002-0.099). These data suggest that the experience of chronic peer victimization during adolescence might induce psychopathology-relevant deviations from normative brain development. Early peer victimization interventions could prevent such pathological changes.
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http://dx.doi.org/10.1038/s41380-018-0297-9DOI Listing
November 2020

Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse.

Am J Psychiatry 2019 02 11;176(2):146-155. Epub 2018 Dec 11.

The Centre for Population Neuroscience and Stratified Medicine and SGDP Centre, Institute of Psychiatry, King's College London (Tay, Macare, Ruggeri, Jia, Chu, Biondo, Ing, Quinlan, Desrivières, Barker, Schumann); the Department of Biochemistry and Molecular Biology, MOE Key Laboratory of Metabolism and Molecular Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China (Liu); the Institute of Science and Technology of Brain-Inspired Intelligence, Fudan University, Shanghai, China (Jia); the Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China (Jia); the School of Life Sciences and Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China (Luo); Uppsala University, Uppsala, Sweden (Sarkysian, Bakalkin); the Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Banaschewski, Hohmann); the Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Barker); the Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin (Bokde, Nees); University Medical Centre Hamburg-Eppendorf, Hamburg, Germany (Bromberg, Büchel); the Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Flor, Nees); the Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany (Flor); the Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Nees); the German Research Foundation, Bonn, Germany (Nees); NeuroSpin, Université Paris-Saclay, Gif-sur-Yvette, France (Frouin, Orfanos); the Departments of Psychiatry and Psychology, University of Vermont, Burlington (Garavan); Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom (Gowland); the Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin (Heinz, Walter); Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Berlin (Itterman); the Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry," DIGITEO Labs, University Paris Sud-Paris Saclay, University Paris Descartes, Gif sur Yvette, France (Martinot); the Maison de Solenn, Cochin Hospital, Paris, France (Martinot); the Institut National de la Santé et de la Recherche Médicale, University Paris Sud-University Paris Saclay, DIGITEO Labs, Gif sur Yvette, France (Artiges); the Department of Psychiatry, Orsay Hospital, Orsay, France (Artiges); the Bloorview Research Institute, Holland Bloorview Kids Rehabilitation, Hospital and Departments of Psychology and Psychiatry, Bloorview Research Institute, University of Toronto, Toronto ( Paus); the Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Poustka); the Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Vienna (Poustka); the Department of Psychiatry and the Neuroimaging Center, Technische Universität Dresden, Dresden, Germany (Fröhner, Smolka); the School of Psychology and the Global Brain Health Institute, Trinity College Dublin, Dublin (Whelan); the Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Hannover, Germany (Frieling, Bleich); the Department of Medical Sciences, Molecular Medicine and Science for Life laboratory, Uppsala University, Uppsala, Sweden (Syvänen); and the Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm (Rüegg, Ekström).

Objective: Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population.

Methods: A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study.

Results: Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use.

Conclusions: Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
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http://dx.doi.org/10.1176/appi.ajp.2018.17121360DOI Listing
February 2019

Shared and unique variances of interpersonal callousness and low prosocial behavior.

Psychol Assess 2019 Mar 10;31(3):376-388. Epub 2018 Dec 10.

Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London.

Although low prosocial behavior (LPB) items have been incorporated into youth measures of callousness, it remains unclear from current factor analytic findings whether callous traits and LPB are best operationalized as a common construct, or distinct dimensions. Using data from a population-representative birth cohort (N = 5,463), this study compared 4 latent factor structures for interpersonal callousness (IC; 6 items) and LPB (5 items) at age 13: (a) unidimensional; (b) two-factor; (c) higher-order (with 2 subfactors); and (d) bifactor (1 general and 2 specific residual factors). Alternative models distinguishing positively and negatively worded items were tested for comparative purposes. To assess the external validity of the factors that emerged from the best-fitting model, associations with early parenting styles and psychiatric comorbidities were examined. A bifactor model, achieving invariance for males and females, offered the best fit for these data. However, additional bifactor-specific indices suggested that the specific IC factor did not offer a unique contribution to the total variance over and above the general factor (IC/LPB). Of the remaining factors, IC/LPB was associated with higher levels of harsh parenting, externalizing and internalizing disorder, and social-cognitive difficulties, and lower levels of warm parenting. The LPB factor, meanwhile, was associated with greater social-cognitive difficulties and externalizing disorder, and lower maternal warmth, evoking a phenotype that may be more indicative of the autism spectrum than IC. These findings suggest that the shared variance underlying IC and LPB taps a severe psychiatric phenotype, while the residual variance for LPB may represent a distinct profile of social-cognitive dysfunction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/pas0000675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558249PMC
March 2019

Dimensionality of Early Adversity and Associated Behavioral and Emotional Symptoms: Data from a Sample of Japanese Institutionalized Children and Adolescents.

Child Psychiatry Hum Dev 2019 06;50(3):425-438

Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny park, London, SE5 8AF, UK.

Recent approaches have begun to identify common variance across co-occurring childhood adversities (CAs) and their associations with symptoms of psychopathology. However, few studies have investigated these questions in high-risk samples, and in different cultural contexts. This study examined common variance amongst 18 types of CAs and associated symptomatology in 457 children and adolescents living in 24 residential homes in Japan. Principal component analysis identified four significant components that explained 35.1% of the variance: parental abuse, parental psychosocial risks, parental absence, and parental neglect. Path analysis revealed general as well as differential associations with negative outcomes: parental abuse, parental neglect, and parental psychosocial risks significantly associated with conduct problems, whereas parental abuse uniquely associated with peer problems, and parental neglect with hyperactivity/inattention. As well as confirming prior knowledge, these findings also extended understanding of these associations to a new cultural context. Future studies should take into account the multidimensional nature when assessing CAs.
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http://dx.doi.org/10.1007/s10578-018-0850-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478638PMC
June 2019

The Earlier the Better? Pausing for Thought ….

Child Dev 2019 01 20;90(1):20-24. Epub 2018 Oct 20.

King's College London.

Is earlier intervention always superior? Using two complementary forms of meta-analysis, Gardner and colleagues find no support for the "earlier is better" hypothesis in outcomes of parenting programs for child behavior problems across the 2-11 year age range. This commentary explores possible methodological and substantive reasons for the pattern of their findings. We need additional careful analyses of this kind, assessing age variations in intervention effects across broader age ranges, and in other developmental domains, for strong tests of the "earlier is better" hypothesis. At this stage, however, Gardner et al.'s findings give us some pause for thought.
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http://dx.doi.org/10.1111/cdev.13168DOI Listing
January 2019

Hidden hypotheses in 'hypothesis-free' genome-wide epigenetic associations.

Curr Opin Psychol 2019 06 25;27:13-17. Epub 2018 Jul 25.

Medical Research Council Integrative Epidemiology Unit and Bristol Medical School, Population Health Sciences, University of Bristol, UK.

The recent interest in epigenetics within mental health research, from a developmental perspective, stems from the potential of DNA methylation to index both exposure to adversity and vulnerability for mental health problems. Genome-wide technology has facilitated epigenome-wide association studies (EWAS), permitting 'hypothesis-free' examinations in relation to adversity and/or mental health problems. In EWAS, rather than focusing on a priori established candidate genes, the genome is screened for DNA methylation, thereby enabling a more comprehensive representation of variation associated with complex disease. Despite their 'hypothesis-free' label, however, results of EWAS are in fact conditional on several a priori hypotheses, dictated by the design of EWAS platforms as well as assumptions regarding the relevance of the biological tissue for mental health phenotypes. In this short report, we review three hidden hypotheses - and provide recommendations - that combined will be useful in designing and interpreting EWAS projects.
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http://dx.doi.org/10.1016/j.copsyc.2018.07.009DOI Listing
June 2019

Inflammation-related epigenetic risk and child and adolescent mental health: A prospective study from pregnancy to middle adolescence.

Dev Psychopathol 2018 08;30(3):1145-1156

King's College London.

In 785 mother-child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7-15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7-15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health.
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http://dx.doi.org/10.1017/S0954579418000330DOI Listing
August 2018
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