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The Genesis 12-19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene-environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date. [ABSTRACT FROM AUTHOR]

Objectives: Negative life events are associated with sleep disturbances. Further understanding of these associations is beneficial as sleep disturbances are common. We assessed the association between two commonly distinguished types of negative life events (dependent vs. independent) and sleep quality. The extent to which genetic and environmental influences explained the association between dependent negative life events and sleep quality was also assessed. Finally, we examined the presence of gene-environment interaction by assessing whether genetic liability to sleep disturbance varied as a function of dependent negative life events.Methods: Structural equation modelling was used to perform the statistical analyses on questionnaire data collected from 1556 twin and non-twin siblings.Results: Poor sleep quality was more strongly associated with dependent as compared to independent negative life events (r=.34 and .15, respectively). There was substantial overlap in the genetic influences on the association between dependent negative life events and poor sleep quality (rA=.62([.43-.81])), suggesting gene-environment correlation. Environmental overlap was small (rE=.16([.04-.28])). Genetic influences accounted for a large proportion of the association (70%([.47-.92])) with the remaining co-variance due to non-shared environment (30%([.08-.53])). Genetic liability to sleep quality was not moderated by dependent negative life events.Conclusions: Genetic and environmental effects on sleep are not necessarily distinct but to some extent work in concert. This should be considered in future studies assessing the genetic and environmental effects on sleep. [ABSTRACT FROM AUTHOR]

BACKGROUND: To investigate the extent to which three putative 'environmental' risk factors, maternal punitive discipline (MPD), paternal punitive discipline (PPD) and negative life events (NLEs), share genetic influences with, and moderate the heritability of, externalizing behavior.MethodThe sample consisted of 2647 participants, aged 12-19 years, from the G1219 and G1219Twins longitudinal studies. Externalizing behavior was measured using the Youth Self-Report, MPD, PPD and exposure to NLEs were assessed using the Negative Sanctions Scale and the Life Event Scale for Adolescents respectively.ResultGenetic influences overlapped for externalizing behavior and each 'environmental' risk, indicating gene-environment correlation. When controlling for the gene-environment correlation, genetic variance decreased, and both shared and non-shared environmental influences increased, as a function of MPD. Genetic variance increased as a function of PPD, and for NLEs the only interaction effect was on the level of non-shared environment influence unique to externalizing behavior.ConclusionThe magnitude of the influence of genetic risk on externalizing behavior is contextually dependent, even after controlling for gene-environment correlation. [ABSTRACT FROM AUTHOR]

Background. Prevalence of childhood anxiety disorders at specific ages and genetic etiological influences on anxiety disorders in young children have been little studied. The present study reports prevalence estimates in a community sample of 6-year-old twins, and patterns of genetic and environmental influences on these early-onset anxiety disorders.Method. Using a two-phase design 4662 twin-pairs were sampled and 854 pairs were assessed in the second phase by maternal-informant diagnostic interview using DSM-IV criteria.Results. The most common conditions were separation anxiety disorder (SAD) [2.8%, 95% confidence interval (CI) 2.1-3.8, for current disorder] and specific phobia (10.8%, 95% CI 8.4-13.6, for current disorder). Behavioral genetic modeling was feasible for these two conditions, applied to two phenotypes: symptom syndrome (regardless of impairment) and the narrower one of diagnostic status (symptom syndrome with associated impairment). The heritability estimate for SAD diagnostic status was high, 73%, with remaining variance attributed to non-shared environment. The heritability estimates for specific phobia were also high, 80% for the symptom syndrome and 60% for diagnostic status, with remaining variance attributed in both cases to non-shared environment.Conclusions. Compared with previous epidemiological surveys of children and adolescents in wide age-bands, the current estimates suggest that rates of anxiety disorders assessed in young childhood are generally at least as high and perhaps higher compared with those found in older children. The heritability estimates suggest that the genetic effects on these early-onset anxiety disorders are substantial and more significant than environmental effects, whether shared or non-shared. [ABSTRACT FROM AUTHOR]

Recent theory proposes that aggressive and nonaggressive antisocial behaviour (ASB) represent different pathways toward delinquency. It has also been suggested that Aggressive ASB is heritable, whereas nonaggressive ASB is more influenced by shared environment.The twin study of child and adolescent development is a Swedish population-based study of 1,480 twin pairs. The present study included 1,226 twin pairs. We used the parental-reported Aggression and Delinquency scales from the CBCL measured at age 8-9. Delinquent behaviour was measured through self-report at age 16-17. We explored how genetic and environmental effects influence the relationships between aspects of ASB in childhood and adolescent delinquency using structural equations modelling.For girls we found that the relationship between Aggressive Behaviour and Self-Reported Delinquency was explained by genetic influences. The correlation between Delinquent Behaviour and Self-Reported Delinquency was due to continuity of genetic influences. For boys, there was no significant mediation between Aggressive Behaviour and Self-Reported Delinquency, but there were significant shared environmental effects on the relationship between Delinquent Behaviour and Self-Reported Delinquency.Our results suggest that there are sex differences in the development of ASB. The hypothesis that the aggressive pathway is genetically mediated was supported in girls, whereas the hypothesis that the nonaggressive pathway is environmentally dependent was supported in boys. [ABSTRACT FROM AUTHOR]

The relation of lexical and grammatical knowledge is at the core of many controversies in linguistics and psycholinguistics. Recent empirical findings that the two are highly correlated in early language development have further energized the theoretical debate. Behavioural genetics provides an illuminating new tool to explore this question, by addressing the question of whether the empirical correlation simply reflects the fact that environments which facilitate one aspect of language growth also facilitate the other, or whether the same underlying acquisition mechanisms, influenced by the same genes, are responsible for the correlation. We explored this issue in a study of 2898 pairs of two-year-old twins born in England and Wales. Language development was assessed by their parents using an adapted version of the MacArthur Communicative Development Inventory which assesses vocabulary and grammar. Moderate heritabilities were found for both. As in previous studies, measures of vocabulary and sentence complexity were substantially correlated (r = 0.66). Behaviour-genetic modelling of the relation of vocabulary and grammar produced an estimated value of 0.61 for the genetic correlation, a measure of the overlap of the genetic effects that contribute to the two aspects of language development. In contrast, a measure of nonverbal cognitive development, the PARCA, was only weakly correlated at both the phenotypic level and at the level of genetic correlations with the language measures. Thus, although the distinction between verbal and nonverbal skills has a genetic basis underlying the phenotypic dissociation, there is little evidence either genetically or phenotypically for a dissociation between vocabulary and grammar within language. [ABSTRACT FROM AUTHOR]

Background: BDD and OCD symptoms often co-occur, but the associations between specific symptoms remain unclear. Furthermore, current research suggests that the clinical presentation of emotional disorders can differ in individuals who self-report exposure to trauma, but it is unclear whether this extends to BDD and OCD. The current study aimed to: (a) investigate associations between individual OCD and BDD symptoms and (b) determine whether symptom networks differ in those with self-reported trauma compared to those without self-reported trauma., Methods: Participants (N = 3127) were drawn from the Genetic Links to Anxiety and Depression (GLAD) Study and had completed validated self-reported questionnaires to assess BDD and OCD symptoms, and childhood and adulthood experiences of trauma. Network analysis was used to investigate associations between seven BDD symptoms and six OCD symptom domains. Networks of reporters and non-reporters of lifetime trauma were compared using the network comparison test., Results: BDD and OCD symptoms clustered distinctively with some bridging associations between them. The strongest bridging edges highlighted an association between three core BDD symptoms and the OCD domain of obsessional thoughts. BDD and OCD networks of reporters and non-reporters of lifetime trauma did not differ., Limitations: Cross-sectional design, meaning causality cannot be inferred., Conclusions: The findings suggest that BDD and OCD symptoms cluster distinctively, with some bridging associations between core BDD symptoms and obsessional thoughts. Future research is needed to understand the mechanisms underpinning this relationship., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations between developmental trajectories of emotional problems and early adult alcohol use behaviors, while considering co-occurring conduct problems, developmental change/timing, sex differences, and potential confounds., Methods: Participants were from the Twins Early Development Study (analytic N = 19,908 individuals). Emotional and conduct problems were measured by parent reports at child ages 4, 7, and 9 years and via self-reports at ages 9, 11, and 16 years on the Strengths and Difficulties Questionnaire. Alcohol use behaviors (alcohol consumption and alcohol-related problems) were self-reported by the twins on the Alcohol Use Disorders Identification Test at age 22 years. Piecewise latent growth curve models described nonlinear developmental trajectories of emotional and conduct problems from ages 4 to 16. At age 22, alcohol use was regressed on emotional and conduct problems' intercepts and slopes from piecewise latent growth curve model and sex differences in regression coefficients were tested. Using twin modeling, Cholesky decompositions and direct path models were compared to test whether significant phenotypic associations were best explained by direct phenotypic influences or correlated genetic and environmental influences., Results: Emotional problems had different associations with alcohol-related problems versus alcohol consumption. After accounting for direct influences from conduct problems, emotional problems were not associated with alcohol-related problems, while emotional problems at age 9 were negatively associated with alcohol consumption in males., Conclusions: Overall, findings did not support emotional problems as prospective risk factors for severe alcohol use above and beyond risks associated with conduct problems. Sex- and age-specific links between emotional problems and alcohol consumption in early adulthood may be worthy of further exploration, particularly as twin analyses improved our confidence that such links may be underpinned by causal mechanisms., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Attention Deficit Hyperactivity Disorder (ADHD) is a common and heritable neurodevelopmental condition that has been the subject of a wealth of genetics research. Because ADHD has an early age of onset, most of this work has focused on children, meaning that less is known about the genetics of ADHD in adults. Additionally, while much research has assessed the heritability of ADHD as a general dimension, less has assessed the heritability of individual subtypes (inattention, hyperactivity) or symptoms of ADHD. It therefore remains unclear whether the genetic factors underlying ADHD symptoms conform to a unidimensional or multidimensional structure. The aim of this study was to assess the genetic and environmental dimensionality of adult ADHD symptoms. We analyzed data from 10,454 twins of the Twins Early Development Study, who provided self-reports of ADHD symptoms using the Conners scale at age 21 years. The data conformed well to a psychometric bifactor model, providing support for a general dimension of ADHD in addition to secondary dimensions for inattention and hyperactivity. However, a bifactor independent pathway twin model provided support for a general dimension only at the level of non-shared environmental effects and not additive genetic or shared environmental effects. This suggests that symptoms of ADHD cluster together under a general dimension of non-shared environmental effects, although the two subtypes of ADHD (inattention and hyperactivity) are meaningfully genetically distinct. We found the overall heritability of ADHD to be 40%, comparable with previous estimates for adult ADHD symptoms. Our results provide useful insights into the genetic and environmental architecture of specific ADHD symptoms., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Mental health problems and traits capturing psychopathology are common and often begin during adolescence. Decades of twin studies indicate that genetic factors explain around 50% of individual differences in adolescent psychopathology. In recent years, significant advances, particularly in genomics, have moved this work towards more translational findings., Methods: This review provides an overview of the past decade of genetically sensitive studies on adolescent development, covering both family and genomic studies in adolescents aged 10-24 years. We focus on five research themes: (1) co-occurrence or comorbidity between psychopathologies, (2) stability and change over time, (3) intergenerational transmission, (4) gene-environment interplay, and (5) psychological treatment outcomes., Results: First, research shows that much of the co-occurrence of psychopathologies in adolescence is explained by genetic factors, with widespread pleiotropic influences on many traits. Second, stability in psychopathology across adolescence is largely explained by persistent genetic influences, whereas change is explained by emerging genetic and environmental influences. Third, contemporary twin-family studies suggest that different co-occurring genetic and environmental mechanisms may account for the intergenerational transmission of psychopathology, with some differences across psychopathologies. Fourth, genetic influences on adolescent psychopathology are correlated with a wide range of environmental exposures. However, the extent to which genetic factors interact with the environment remains unclear, as findings from both twin and genomic studies are inconsistent. Finally, a few studies suggest that genetic factors may play a role in psychological treatment response, but these findings have not yet been replicated., Conclusions: Genetically sensitive research on adolescent psychopathology has progressed significantly in the past decade, with family and twin findings starting to be replicated at the genomic level. However, important gaps remain in the literature, and we conclude by providing suggestions of research questions that still need to be addressed., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: The identification of predictors of treatment response is crucial for improving treatment outcome for children with anxiety disorders. Machine learning methods provide opportunities to identify combinations of factors that contribute to risk prediction models., Methods: A machine learning approach was applied to predict anxiety disorder remission in a large sample of 2114 anxious youth (5-18 years). Potential predictors included demographic, clinical, parental, and treatment variables with data obtained pre-treatment, post-treatment, and at least one follow-up., Results: All machine learning models performed similarly for remission outcomes, with AUC between 0.67 and 0.69. There was significant alignment between the factors that contributed to the models predicting two target outcomes: remission of all anxiety disorders and the primary anxiety disorder. Children who were older, had multiple anxiety disorders, comorbid depression, comorbid externalising disorders, received group treatment and therapy delivered by a more experienced therapist, and who had a parent with higher anxiety and depression symptoms, were more likely than other children to still meet criteria for anxiety disorders at the completion of therapy. In both models, the absence of a social anxiety disorder and being treated by a therapist with less experience contributed to the model predicting a higher likelihood of remission., Conclusions: These findings underscore the utility of prediction models that may indicate which children are more likely to remit or are more at risk of non-remission following CBT for childhood anxiety.

Anxiety sensitivity may be associated with both anxiety and eating disorder symptoms, which could contribute to the frequent comorbidity of both syndromes. This study examined the common (i.e., correlated) genetic and environmental contributions to anxiety sensitivity, cognitive symptoms of eating disorder severity, and anxiety symptoms to understand their co-occurrence in adolescence. This study analyzed data from the Twins Early Development Study. When twins were 16 years old (N = 5,111 pairs), they self-reported anxiety sensitivity via the Child Anxiety Sensitivity Index and cognitive symptoms of eating disorder severity via four items from the Eating Disorder Diagnostic Scale. Parents reported adolescent anxiety symptoms via the Anxiety Related Behaviour Questionnaire. Common genetic and non-shared environmental factors contributed to phenotypic correlations among cognitive symptoms of eating disorders. Genetic and nonshared environmental influences contributed to anxiety sensitivity and a latent variable of cognitive symptoms of eating disorder severity. Genetic, shared-, and nonshared- environmental influences contributed to anxiety symptoms. Common genetic and nonshared environmental influences contributed to anxiety sensitivity and anxiety symptoms, as well as anxiety sensitivity and cognitive symptoms of eating disorder severity. However, there was no evidence of common genetic or environmental contributions to anxiety symptoms and cognitive symptoms of eating disorder severity. This study implicates anxiety sensitivity as a potential cognitive process associated with both anxiety symptoms and cognitive symptoms of eating disorders., Competing Interests: Compliance with Ethical Standards. Funding: The Twins Early Development Study (TEDS) is supported by a programme grant from the UK Medical Research Council [MR/V012878/1 and previously MR/M021475/1]; this work was also supported by the Joseph-Armand Bombardier Canada Graduate Scholarship – Master’s to Ms. Smail-Crevier. Conflict of Interest: The authors have no relevant financial or non-financial interests to disclose. Ethics Approval: This study was cleared by the University of Windsor Research Ethics Board. Informed Consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment., Methods: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors., Results: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group., Conclusions: Sub-optimal response patterns can be partially differentiated using variables assessed at pre-treatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decision-making and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Childhood maltreatment and intimate partner violence (IPV) victimization are major psychiatric risk factors. Maltreatment substantially increases the likelihood of subsequent IPV victimization, but what drives this association is poorly understood. We analyzed retrospective self-reports of maltreatment and IPV victimization in 12,794 participants (58% women, 42% men) from the Twins Early Development Study at ages 21 and 26 using quantitative genetic methods. We estimated the etiological influences common to maltreatment and IPV, and the effect of maltreatment on IPV beyond such common influences. Participants who reported childhood maltreatment ( ~ 7% of the sample) were 3 times more likely than their peers to also report IPV victimization at age 21, 4 times more likely at 26. The association between maltreatment and IPV was mostly due to environmental influences shared by co-twins (42-43%) and genetic influences (30-33%), as well as nonshared environmental influences (25-27%). The association between maltreatment and IPV was similar for women and men, but its etiology partly differed by sex. Maltreatment had a moderate effect on IPV in phenotypic models (β = 0.25-0.30), decreasing to a small-to-moderate range in causally informative models accounting for their common etiology (β = 0.15-0.21). Risk factors common to maltreatment and IPV victimization are largely familial in origin, environmental and genetic. Even considering common risk factors, experiencing maltreatment may be causally related to subsequent IPV victimization. Interventions promoting safe intimate relationships among young adults exposed to maltreatment are warranted and should address family-level environmental risk and individual-level risk shaped by genetics., (© 2024. The Author(s).)

Background: Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population., Methods: Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample., Results: Prenatal alcohol exposure (β = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (β = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06-1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21-2.34, p = .002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (β = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (β = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history., Limitations: Familial confounding could not be fully adjusted for. Rater reports include some biases., Conclusions: These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Studies on polygenic risk for psychiatric traits commonly use a disorder-level approach to phenotyping, implicitly considering disorders as homogeneous constructs; however, symptom heterogeneity is ubiquitous, with many possible combinations of symptoms falling under the same disorder umbrella. Focusing on individual symptoms may shed light on the role of polygenic risk in psychopathology., Objective: To determine whether polygenic scores are associated with all symptoms of psychiatric disorders or with a subset of indicators and whether polygenic scores are associated with comorbid phenotypes via specific sets of relevant symptoms., Design, Setting, and Participants: Data from 2 population-based cohort studies were used in this cross-sectional study. Data from children in the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in the primary analysis, and data from children in the Twins Early Development Study (TEDS) were included in confirmatory analyses. Data analysis was conducted from October 2021 to January 2024. Pregnant women based in the Southwest of England due to deliver in 1991 to 1992 were recruited in ALSPAC. Twins born in 1994 to 1996 were recruited in TEDS from population-based records. Participants with available genetic data and whose mothers completed the Short Mood and Feelings Questionnaire and the Strength and Difficulties Questionnaire when children were 11 years of age were included., Main Outcomes and Measures: Psychopathology relevant symptoms, such as hyperactivity, prosociality, depression, anxiety, and peer and conduct problems at age 11 years. Psychological networks were constructed including individual symptoms and polygenic scores for depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), body mass index (BMI), and educational attainment in ALSPAC. Following a preregistered confirmatory analysis, network models were cross-validated in TEDS., Results: Included were 5521 participants from ALSPAC (mean [SD] age, 11.8 [0.14] years; 2777 [50.3%] female) and 4625 participants from TEDS (mean [SD] age, 11.27 [0.69] years; 2460 [53.2%] female). Polygenic scores were preferentially associated with restricted subsets of core symptoms and indirectly associated with other, more distal symptoms of psychopathology (network edges ranged between r = -0.074 and r = 0.073). Psychiatric polygenic scores were associated with specific cross-disorder symptoms, and nonpsychiatric polygenic scores were associated with a variety of indicators across disorders, suggesting a potential contribution of nonpsychiatric traits to comorbidity. For example, the polygenic score for ADHD was associated with a core ADHD symptom, being easily distracted (r = 0.07), and the polygenic score for BMI was associated with symptoms across disorders, including being bullied (r = 0.053) and not thinking things out (r = 0.041)., Conclusions and Relevance: Genetic associations observed at the disorder level may hide symptom-level heterogeneity. A symptom-level approach may enable a better understanding of the role of polygenic risk in shaping psychopathology and comorbidity.

Greater environmental sensitivity has been associated with increased risk of mental health problems, especially in response to stressors, and lower levels of subjective wellbeing. Conversely, sensitivity also correlates with lower risk of emotional problems in the absence of adversity, and in response to positive environmental influences. Additionally, sensitivity has been found to correlate positively with autistic traits. Individual differences in environmental sensitivity are partly heritable, but it is unknown to what extent the aetiological factors underlying sensitivity overlap with those on emotional problems (anxiety and depressive symptoms), autistic traits and wellbeing. The current study used multivariate twin models and data on sensitivity, emotional problems, autistic traits, and several indices of psychological and subjective wellbeing, from over 2800 adolescent twins in England and Wales. We found that greater overall sensitivity correlated with greater emotional problems, autistic traits, and lower subjective wellbeing. A similar pattern of correlations was found for the Excitation and Sensory factors of sensitivity, but, in contrast, the Aesthetic factor was positively correlated with psychological wellbeing, though not with emotional problems nor autistic traits. The observed correlations were largely due to overlapping genetic influences. Importantly, genetic influences underlying sensitivity explained between 2 and 12% of the variations in emotional problems, autistic traits, and subjective wellbeing, independent of trait-specific or overlapping genetic influences. These findings encourage incorporating the genetics of environmental sensitivity in future genomic studies aiming to delineate the heterogeneity in emotional problems, autistic traits, and wellbeing., (© 2024. The Author(s).)

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies., Competing Interests: Per Hoffmann receives Salary from the Life & Brain GmbH, Bonn, Germany. James L. Kennedy is a member of the Scientific Advisory Board for Myriad Neuroscience Inc. Ian B. Hickie was an inaugural Commissioner on Australia’s National Mental Health Commission (2012-18). He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M Australian Government-funded Project Synergy (2017-20; a three-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. Andrew M. Mcintosh has received research support from Eli Lilly, Janssen, and The Sackler Trust. AMM has also received speaker fees from Illumina and Janssen. Murray B. Stein has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, Boehringer Ingelheim, Bionomics, BioXcel Therapeutics, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He is paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. Joel Gelernter is named as an inventor on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018 and issued on January 26, 2021 as U.S. Patent No. 10,900,082; and is paid for editorial work for the journal “Complex Psychiatry.” Iiris Hovatta received speaker’s honoraria from Lundbeck. Ole A. Andreassen received speaker’s honorarium from Lundbeck and Sunovion, consultant for Cortechs.ai and Precision Health AS. Katharina Domschke has been a member of the Steering Committee Neurosciences, Janssen, Inc. until 2022 and is currently a member of the Board of the German National Society of Psychiatry (DGPPN) and the Neurotorium Editorial Board of the Lundbeck Foundation. Jordan W. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity) and has received an honorarium for an internal seminar Tempus Labs. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Eduard Maron has received research support and has also received speaker fees from Lundbeck. Hans J. Grabe has received travel grants and speakers honoraria from Indorsia, Neuraxpharm, Servier and Janssen Cilag. Henrik Larsson has served as a speaker for Evolan Pharma, Medici and Shire/Takeda and has received research grants from Shire/Takeda; all outside the submitted work. Gerome Breen is an advisory board member for Compass Pathways. Jürgen Deckert is a member of the board of the German Society of Biological Psychiatry and is on the scientific advisory boards of non-profit organizations and foundations. Volker Arolt worked as an advisor for Sanofi-Adventis Germany. Zach Fuller and Xin Wang are employees of 23andMe and hold stock or stock options in 23andMe. All other authors have no competing interests to declare.

Childhood maltreatment and intimate partner violence (IPV) victimization are major psychiatric risk factors. Maltreatment substantially increases the likelihood of subsequent IPV victimization, but what drives this association is poorly understood. We analyzed retrospective self-reports of maltreatment and IPV in 12794 participants (58% women, 42% men) from the Twins Early Development Study at ages 21 and 26 using quantitative genetic methods. We estimated the etiological influences common to maltreatment and IPV, and the direct causal effect of maltreatment on IPV beyond such common influences. Participants exposed to maltreatment (~7% of the sample) were 3 times more likely to experience IPV victimization than their peers at age 21, 4 times more likely at 26. The association between maltreatment and IPV was mostly due to environmental influences shared by co-twins (42-43%) and genetic influences (30-33%). The association between maltreatment and IPV was similar for women and men, but its etiology partly differed by sex. Maltreatment had a moderate-to-large effect on IPV in phenotypic models ( β = 0.23-0.34), decreasing to a small-to-moderate range in causal models accounting for their common etiology ( β = 0.15-0.21). Risk factors common to maltreatment and IPV victimization are largely familial in origin, environmental and genetic. Even considering common risk factors, experiencing maltreatment is causally related to subsequent IPV victimization. Interventions promoting safe intimate relationships among young adults exposed to maltreatment are warranted and should address family-level environmental risk and individual-level risk shaped by genetics., Competing Interests: Conflicts of interest The authors declare no financial disclosures or competing interests.

Objective: The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide. This article serves the dual function of providing an in-depth description of our study protocol and of describing our initial sample including demographics, diagnoses, and physical and psychiatric comorbidities., Method: EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies., Results: As of September 2022, EDGI UK recruited 7435 survey participants: 98% female, 93.1% white, 97.8% cisgender, 65.9% heterosexual, and 52.1% have a university degree. Over half (57.8%) of these participants have returned their saliva DNA kit. The most common diagnoses are anorexia nervosa (48.3%), purging disorder (37.8%), bulimia nervosa (37.5%), binge-eating disorder (15.8%), and atypical anorexia nervosa (7.8%)., Conclusion: EDGI UK is the largest UK eating disorders study and efforts to increase its diversity are underway. It offers a unique opportunity to accelerate eating disorder research. Researchers and participants with lived experience can collaborate on projects with unparalleled sample size., Public Significance Statement: Eating disorders are debilitating and costly for society but are under-researched due to underfunding. EDGI UK is one of the largest eating disorder studies worldwide with ongoing recruitment. The collected data constitute a resource for secondary analysis. We will combine data from all international EDGI branches and the NIHR BioResource to facilitate research that improves our understanding of eating disorders and their comorbidities., (© 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Background: The association between weight and depressive symptoms is well established, but the direction of effects remains unclear. Most studies rely on body mass index (BMI) as the sole weight indicator, with few examining the aetiology of the association between weight indicators and depressive symptoms., Methods: We analysed data from the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK) (7658 and 2775 twin pairs, respectively). A phenotypic cross-lagged panel model assessed the directionality between BMI and depressive symptoms at ages 12, 16, and 21 years in TEDS. Bivariate correlations tested the phenotypic association between a range of weight indicators and depressive symptoms in TwinsUK. In both samples, structural equation modelling of twin data investigated genetic and environmental influences between weight indicators and depression. Sensitivity analyses included two-wave phenotypic cross-lagged panel models and the exclusion of those with a BMI <18.5., Results: Within TEDS, the relationship between BMI and depression was bidirectional between ages 12 and 16 with a stronger influence of earlier BMI on later depression. The associations were unidirectional thereafter with depression at 16 influencing BMI at 21. Small genetic correlations were found between BMI and depression at ages 16 and 21, but not at 12. Within TwinsUK, depression was weakly correlated with weight indicators; therefore, it was not possible to generate precise estimates of genetic or environmental correlations., Conclusions: The directionality of the relationship between BMI and depression appears to be developmentally sensitive. Further research with larger genetically informative samples is needed to estimate the aetiological influence on these associations.

The COVID-19 pandemic brought about dramatic changes in how patients access healthcare from its outset. Lockdown restrictions and remote working led to a proliferation of digital technologies and services, which also impacted mental health provisions. Against the backdrop of new and changing support services, along with an unprecedented emphasis on mental health, relatively little is known about how adults sought out and received support for their mental health during this period. With a sample of 27,574 adults assessed longitudinally online over 12 months of the pandemic in the UK, we analysed reports of help-seeking for mental health, as well as sources of treatment or support and the perceived helpfulness of treatments received. We observed that the proportions of participants who reported seeking help remained relatively consistent throughout the 12-month period (ranging from 12.6% to 17.0%). Online talking therapies were among the most frequently sought sources (15.3%), whereas online self-guided treatments were among the least frequently sought sources (5%). Telephone lines, both NHS and non-governmental, had marked treatment 'gaps'. These treatment gaps, where individuals sought treatment but did not receive it, were especially evident for men and older adults. Our findings underscore online talking therapies as being a widely-sought and helpful source of mental health support. This is important given the current global need for accessible treatment options., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Parsons et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical 'splitting' and 'lumping' approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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 adolescents suffer from persisting emotional symptoms. However, the role of different types of interpersonal difficulties, such as social isolation and peer victimisation, in these reciprocal associations is still unclear. In addition, the lack of longitudinal twin studies conducted on emotional symptoms during adolescence means that the genetic and environmental contributions to these relationships during adolescence remain unknown., Methods: Participants (N = 15,869) from the Twins Early Development Study completed self-reports of emotional symptoms, social isolation and peer victimisation at 12, 16 and 21 years old. A phenotypic cross-lagged model examined reciprocal associations between variables over time, and a genetic extension of this model examined the aetiology of the relationships between variables at each timepoint., Results: First, emotional symptoms were reciprocally and independently associated with both social isolation and peer victimisation over time, indicating that different forms of interpersonal difficulties uniquely contributed to emotional symptoms during adolescence and vice versa. Second, early peer victimisation predicted later emotional symptoms via social isolation in mid-adolescence, indicating that social isolation may constitute an intermediate pathway through which peer victimisation predicts longer-term emotional symptoms. Finally, individual differences in emotional symptoms were mostly accounted for by non-shared environmental factors at each timepoint, and both gene-environment and individual-specific environmental mechanisms were involved in the relationships between emotional symptoms and interpersonal difficulties., Conclusions: Our study highlights the necessity to intervene early in adolescence to prevent the escalation of emotional symptoms over time and to consider social isolation and peer victimisation as important risk factors for the long-term persistence of emotional symptoms., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)