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Introduction: Exposure to discrimination has emerged as a risk factor for obesity. It remains unclear, however, whether the genotype of the individual can modulate the sensitivity or response to discrimination exposure (gene × environment interaction) or increase the likelihood of experiencing discrimination (gene-environment correlation)., Methods: This was an observational study of 4,102 white/European Americans in the Health and Retirement Study with self-reported, biological assessments, and genotyped data from 2006 to 2014. Discrimination was operationalized using the average of nine Everyday Discrimination Scale items. Polygenic risk scores (PRSs) for body mass index (BMI) and waist circumference (WC) were calculated using the weighted sum of risk alleles based on studies conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium., Results: We found that greater PRS-BMI was significantly associated with more reports of discrimination (β = 0.04 ± 0.02; p = 0.037). Further analysis showed that measured BMI partially mediated the association between PRS-BMI and discrimination. There was no evidence that the association between discrimination and BMI, or the association between discrimination and WC, differed by PRS-BMI or PRS-WC, respectively., Conclusion: Our findings suggest that individuals with genetic liability for obesity may experience greater discrimination in their lifetime, consistent with a gene-environment correlation hypothesis. There was no evidence of a gene-environment interaction. More genome-wide association studies in diverse populations are needed to improve generalizability of study findings. In the meantime, prevention and clinical intervention efforts that seek to reduce exposure to all forms of discrimination may help reduce obesity at the population level., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Addressing social disparities in health and well-being requires understanding how the effects of discrimination become biologically embedded, and how embedding processes might vary across different demographic contexts. Emerging research suggests that a threat-related gene expression response may contribute to social disparities in health. We tested a contextual vulnerability model of discrimination embedding using an empirical intersectionality (interaction discovery) analysis of pro-inflammatory gene expression in a national sample of non-institutionalized, English-speaking adults with RNA biomarker data (n = 543). At the time of data collection, the average age of participants was 55 years (SD = 13.26) and approximately half identified as female (50.46%). Most participants identified as White (∼73%) and had some college experience (∼60%). Results showed significant variation in the strength of association between daily discrimination and inflammatory gene expression by race and sex ( b  = -0.022; 95% CI:-0.038,-0.005, p  = .009) with the estimated marginal association larger for racially-minoritized males ( b  = 0.007; 95% CI:-0.003,0.017, p  = .163), compared to White males ( b  = -0.006; 95% CI:-0.013,0.001, p  = .076). This study indicates that the link between daily discrimination and inflammatory gene expression may vary by sociodemographic characteristics. To improve initiatives and policies aimed at ameliorating disparities within populations, greater attention is needed to understand how interlocking systems of inequalities contribute to physiological health., Competing Interests: The authors have no conflict of interest., (© 2022 The Authors.)

Background: An ongoing positive revolution advocates a new approach to the individual differences in human emotions, cognitions, and behavior that cause distress and impair functioning. This revolution endorses the long-proposed, but still unrealized rejection of the medical model, which attributes psychological problems to a sick brain or mind. In addition, it advocates replacing the binary diagnoses used in ICD and DSM, which assume a clear discontinuity between "normal" and "abnormal" functioning, with continuous dimensions of psychological problems., Method: Selective literature review., Results and Discussion: Seven strong reasons are provided for adopting a dimensional approach., Competing Interests: Benjamin B. Lahey and Henning Tiemeier both serve on the JCPP Advances Editorial Advisory Board. Robert F. Krueger declares that they have no competing or potential conflicts of interest., (© 2022 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and across clinicians. This paper reviews evidence on the validity and utility of the internalizing and somatoform spectra of HiTOP, which together provide support for an emotional dysfunction superspectrum. These spectra are composed of homogeneous symptom and maladaptive trait dimensions currently subsumed within multiple diagnostic classes, including depressive, anxiety, trauma-related, eating, bipolar, and somatic symptom disorders, as well as sexual dysfunction and aspects of personality disorders. Dimensions falling within the emotional dysfunction superspectrum are broadly linked to individual differences in negative affect/neuroticism. Extensive evidence establishes that dimensions falling within the superspectrum share genetic diatheses, environmental risk factors, cognitive and affective difficulties, neural substrates and biomarkers, childhood temperamental antecedents, and treatment response. The structure of these validators mirrors the quantitative structure of the superspectrum, with some correlates more specific to internalizing or somatoform conditions, and others common to both, thereby underlining the hierarchical structure of the domain. Compared to traditional diagnoses, the internalizing and somatoform spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and greater clinical applicability. Validated measures are currently available to implement the HiTOP system in practice, which can make diagnostic classification more useful, both in research and in the clinic., (© 2022 World Psychiatric Association.)

Perceptions of spiteful behavior are common, distinct from rational fear, and may undergird persecutory ideation. To test this hypothesis and investigate neural mechanisms of persecutory ideation, we employed a novel economic social decision-making task, the Minnesota Trust Game (MTG), during neuroimaging in patients with schizophrenia (n = 30) and community monozygotic (MZ) twins (n = 38; 19 pairs). We examined distinct forms of mistrust, task-related brain activation and connectivity, and investigated relationships with persecutory ideation. We tested whether co-twin discordance on these measurements was correlated to reflect a common source of underlying variance. Across samples persecutory ideation was associated with reduced trust only during the suspiciousness condition, which assessed spite sensitivity given partners had no monetary incentive to betray. Task-based activation contrasts for specific forms of mistrust were limited and unrelated to persecutory ideation. However, task-based connectivity contrasts revealed a dorsal cingulate anterior insula network sensitive to suspicious mistrust, a left frontal-parietal (lF-P) network sensitive to rational mistrust, and a ventral medial/orbital prefrontal (vmPFC/OFC) network that was sensitive to the difference between these forms of mistrust (all p < .005). Higher persecutory ideation was predicted only by reduced connectivity between the vmPFC/OFC and lF-P networks (p = .005), which was only observed when the intentions of the other player were relevant. Moreover, co-twin differences in persecutory ideation predicted co-twin differences in both spite sensitivity and in vmPFC/OFC-lF-P connectivity. This work found that interconnectivity may be particularly important to the complex neurobiology underlying persecutory ideation, and that unique environmental variance causally linked persecutory ideation, decision-making, and brain connectivity., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Traditionally, personality has been conceptualized in terms of dimensions of human experience - habitual ways of thinking, feeling, and behaving. By contrast, psychopathology has traditionally been conceptualized in terms of categories of disorder - disordered thinking, feeling, and behaving. The empirical literature, however, routinely shows that psychopathology does not coalesce into readily distinguishable categories. Indeed, psychopathology tends to delineate dimensions that are relatively similar to dimensions of personality. In this special issue of Personality Neuroscience , authors took up the challenge of reconceptualizing personality and psychopathology in terms of connected and interrelated dimensions, and they considered the utility of pursuing neuroscientific inquiry from this more integrative perspective. In this editorial article, we provide the relevant background to the interface between personality, psychopathology, and neuroscience; summarize contributions to the special issue; and point toward directions for continued research and refinement. All told, it is evident that quantitatively derived, integrative models of personality-psychopathology represent a particularly promising conduit for advancing our understanding of the neurobiological foundation of human experience, both functional and dysfunctional., (© The Author(s) 2021.)

Importance: Wealthy adults tend to live longer than those with less wealth. However, a challenge in this area of research has been the reduction of potential confounding by factors associated with the early environment and heritable traits, which could simultaneously affect socioeconomic circumstances in adulthood and health across the life course., Objective: To identify the association between net worth at midlife and subsequent all-cause mortality in individuals as well as within siblings and twin pairs., Design Setting and Participants: This cohort study conducted a series of analyses using data from the Midlife in the United States (MIDUS) study, an ongoing national study of health and aging. The sample included adults (unrelated individuals, full siblings, and dizygotic and monozygotic twins) aged 20 to 75 years, who participated in wave 1 of the MIDUS study, which occurred from 1994 to 1996. The analyses were conducted between November 16, 2019, and May 18, 2021., Exposures: Self-reported net worth (total financial assets minus liabilities) at midlife (the middle years of life)., Main Outcomes and Measures: All-cause mortality was tracked over nearly 24 years of follow-up, with a censor date of October 31, 2018. Survival models tested the association between net worth and all-cause mortality. Discordant sibling and twin analyses compared longevity within siblings and twin pairs who, given their shared early experiences and genetic backgrounds, were matched on these factors., Results: The full sample comprised 5414 participants, who had a mean (SD) age of 46.7 (12.7) years and included 2766 women (51.1%). Higher net worth was associated with lower mortality risk (hazard ratio [HR], 0.95; 95% CI, 0.94-0.97; P  < .001). Among siblings and twin pairs specifically (n = 2490), a similar within-family association was observed between higher net worth and lower mortality (HR, 0.94; 95% CI, 0.91-0.97; P  = .001), suggesting that the sibling or twin with more wealth tended to live longer than their co-sibling or co-twin with less wealth. When separate estimates were performed for the subsamples of siblings (HR, 0.94; 95% CI, 0.90-0.97; P  = .002), dizygotic twins (HR, 0.94; 95% CI, 0.86-1.02; P  = .19), and monozygotic twins (HR, 0.95; 95% CI, 0.87-1.04; P  = .34), the within-family estimates of the net worth-mortality association were similar, although the precision of estimates was reduced among twins., Conclusions and Relevance: This cohort study found that wealth accumulation at midlife was associated with longevity in US adults. Discordant sibling analyses suggested that this association is unlikely to be simply an artifact of early experiences or heritable characteristics shared by families., Competing Interests: Conflict of Interest Disclosures: Dr Krueger reported receiving grants from the National Institute on Aging (NIA) during the conduct of the study and outside the submitted work. Dr Miller reported receiving grants from the National Institutes of Health (NIH) outside the submitted work. No other disclosures were reported., (Copyright 2021 Finegood ED et al. JAMA Health Forum.)

Previous studies have documented the utility of a transdiagnostic internalizing factor in predicting important future outcomes (e.g., subsequent mental disorder diagnoses). To date, however, no study has investigated whether an internalizing factor predicts mortality risk. Also, while pre-vious studies of mortality risk have emphasized its associations with particular internalizing disorders, no study has assessed how the transdiagnostic internalizing factor vs. disorder-specific variance differently predict that risk. The primary aims of this study were to explore: a) whether the internalizing factor predicts mortality risk, b) whether particular internalizing psychopathologies uniquely predict mortality risk over and beyond the transdiagnostic internalizing factor, and c) whether there is a significant interaction of internalizing with self-reported health in the prediction of mortality risk. We utilized a large national sample of American adults from the Midlife in the United States (MIDUS), a longitudinal study that examined midlife development of individuals across multiple waves between 1995 and 2015. Data were analyzed for the 6,329 participants who completed the phone interview and self-administered questionnaire in MIDUS 1 (1995-1996) and were then followed up until October 31, 2015 or until death. To investigate the association between internalizing and mortality risk, we used the semi-parametric proportional hazards Cox model, where survival time was regressed on a latent internalizing factor. Overall findings indicate that a transdiagnostic internalizing factor significantly predicts mortality risk over a 20-year period (hazard ratio, HR=1.12, 95% CI: 1.05-1.16, p<0.01) and that internalizing outperforms disorder-specific variance (e.g., depression-specific variance) in the prediction of that risk. Further, there was a significant interaction between transdiagnostic internalizing and self-reported health, whereby internalizing psychopathology had a specific association with early death for individuals with excellent self-reported health condition (HR=1.50, 95% CI: 1.17-1.84, p<0.05). This highlights the clinical utility of using the transdiagnostic internalizing factor for prediction of an important future outcome, and supports the argument that internalizing psychopathology can be a meaningful liability to explore in public health practice., (© 2021 World Psychiatric Association.)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co-occurrence in the modal case, heterogeneity of presentation within dis-orders, and instability of diagnosis within patients. This paper reviews the evidence on the validity and utility of the disinhibited externalizing and antagonistic externalizing spectra of HiTOP, which together constitute a broad externalizing superspectrum. These spectra are composed of elements subsumed within a variety of mental disorders described in recent DSM nosologies, including most notably substance use disorders and "Cluster B" personality disorders. The externalizing superspectrum ranges from normative levels of impulse control and self-assertion, to maladaptive disinhibition and antagonism, to extensive polysubstance involvement and personality psychopathology. A rich literature supports the validity of the externalizing superspectrum, and the disinhibited and antagonistic spectra. This evidence encompasses common genetic influences, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, and treatment response. The structure of these validators mirrors the structure of the phenotypic externalizing superspectrum, with some correlates more specific to disinhibited or antagonistic spectra, and others relevant to the entire externalizing superspectrum, underlining the hierarchical structure of the domain. Compared with traditional diagnostic categories, the externalizing superspectrum conceptualization shows improved utility, reliability, explanatory capacity, and clinical applicability. The externalizing superspectrum is one aspect of the general approach to psychopathology offered by HiTOP and can make diagnostic classification more useful in both research and the clinic., (© 2021 World Psychiatric Association.)

An established body of research indicates that discrimination is associated with increased symptoms of anxiety and negative affect. However, the association cannot be interpreted unambiguously as an exposure effect because a common set of genetic factors can simultaneously contribute to increased liability for symptoms of anxiety, negative affect, and the perception of discrimination. The present study elucidates the association between discrimination and anxiety/negative affect by implementing strict genetic controls in a large sample of adults. We used data from the biomarker project of the Study of Midlife Development in the United States (MIDUS), a national probability sample of noninstitutionalized, English-speaking respondents aged 25 to 74 y. Participants who consented to provide genetic data were biologically unrelated and of European ancestry as determined by genotype principal components analysis ( n = 1,146). A single structural regression model was fit to the data with three measures of discrimination specified to load onto a latent factor and six measures of anxiety and negative affect specified to load onto a second latent factor. After accounting for potential genetic confounds-polygenic scores for anxiety, depression, and neuroticism and the first five genetic principal components-greater discrimination was associated with greater anxiety/negative affect (β = 0.53, SE = 0.04, P < 0.001). Findings suggest that measures of perceived discrimination should be considered environmental risk factors for anxiety/negative affect rather than indices of genetic liability for anxiety, depression, or neuroticism. Clinical interventions and prevention measures should focus on ways to mitigate the impact of discrimination to improve mental health at the population level., Competing Interests: The authors declare no competing interest.

Objective: Subthreshold psychosis risk symptoms in the general population may be associated with molecular genetic risk for psychosis. This study sought to optimize the association of risk symptoms with genetic risk for psychosis in a large population-based cohort in the UK (N = 9104 individuals 18-65 years of age) by properly accounting for population stratification, factor structure, and sex., Methods: The newly expanded Generation Scotland: Scottish Family Health Study includes 5391 females and 3713 males with age M [SD] = 45.2 [13] with both risk symptom data and genetic data. Subthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B) and calculation of polygenic risk for schizophrenia was based on 11 425 349 imputed common genetic variants passing quality control. Follow-up examination of other genetic risks included attention-deficit hyperactivity disorder (ADHD), autism, bipolar disorder, major depression, and neuroticism., Results: Empirically derived symptom factor scores reflected interpersonal/negative symptoms and were positively associated with polygenic risk for schizophrenia. This signal was largely sex specific and limited to males. Across both sexes, scores were positively associated with neuroticism and major depressive disorder., Conclusions: A data-driven phenotypic analysis enabled detection of association with genetic risk for schizophrenia in a population-based sample. Multiple polygenic risk signals and important sex differences suggest that genetic data may be useful in improving future phenotypic risk assessment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a 2  = 0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c 2  = 0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a 2  = 0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a 2  = 0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c 2  = 0.31; 0.29-0.33 and c 2  = 0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a scientific effort to address shortcomings of traditional mental disorder diagnoses, which suffer from arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. This paper synthesizes evidence on the validity and utility of the thought disorder and detachment spectra of HiTOP. These spectra are composed of symptoms and maladaptive traits currently subsumed within schizophrenia, other psychotic disorders, and schizotypal, paranoid and schizoid personality disorders. Thought disorder ranges from normal reality testing, to maladaptive trait psychoticism, to hallucinations and delusions. Detachment ranges from introversion, to maladaptive detachment, to blunted affect and avolition. Extensive evidence supports the validity of thought disorder and detachment spectra, as each spectrum reflects common genetics, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, biomarkers, and treatment response. Some of these characteristics are specific to one spectrum and others are shared, suggesting the existence of an overarching psychosis superspectrum. Further research is needed to extend this model, such as clarifying whether mania and dissociation belong to thought disorder, and explicating processes that drive development of the spectra and their subdimensions. Compared to traditional diagnoses, the thought disorder and detachment spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and higher acceptability to clinicians. Validated measures are available to implement the system in practice. The more informative, reliable and valid characterization of psychosis-related psychopathology offered by HiTOP can make diagnosis more useful for research and clinical care., (© 2020 World Psychiatric Association.)

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures than traditional categorical diagnoses given its enhanced reliability. However, one complication is that observed biological correlates of clinical symptoms can reflect various factors, ranging from dispositional risk to consequences of psychopathology. In this paper, we argue that the HiTOP model provides an optimized framework for conducting research on the biological correlates of psychopathology from an ontogenetic perspective that distinguishes among indicators of liability, current symptoms, and consequences of illness. Through this approach, neurobiological research can contribute more effectively to identifying individuals at high dispositional risk, indexing treatment-related gains, and monitoring the consequences of mental illness, consistent with the aims of the HiTOP framework.
., (© 2019, AICHServier GroupCopyright © 2019 AICH Servier Group. All rights reserved.)

Background: Conceptualizations of personality disorders (PD) are increasingly moving towards dimensional approaches. The definition and assessment of borderline personality disorder (BPD) in regard to changes in nosology are of great importance to theory and practice as well as consumers. We studied empirical connections between the traditional DSM-5 diagnostic criteria for BPD and Criteria A and B of the Alternative Model for Personality Disorders (AMPD)., Method: Raters of varied professional backgrounds possessing substantial knowledge of PDs ( N  = 20) characterized BPD criteria with the four domains of the Level of Personality Functioning Scale (LPFS) and 25 pathological personality trait facets. Mean AMPD values of each BPD criterion were used to support a nosological cross-walk of the individual BPD criteria and study various combinations of BPD criteria in their AMPD translation. The grand mean AMPD profile generated from the experts was compared to published BPD prototypes that used AMPD trait ratings and the DSM-5-III hybrid categorical-dimensional algorithm for BPD. Divergent comparisons with DSM-5-III algorithms for other PDs and other published PD prototypes were also examined., Results: Inter-rater reliability analyses showed generally robust agreement. The AMPD profile for BPD criteria rated by individual BPD criteria was not isomorphic with whole-person ratings of BPD, although they were highly correlated. Various AMPD profiles for BPD were generated from theoretically relevant but differing configurations of BPD criteria. These AMPD profiles were highly correlated and showed meaningful divergence from non-BPD DSM-5-III algorithms and other PD prototypes., Conclusions: Results show that traditional DSM BPD diagnosis reflects a common core of PD severity, largely composed of LPFS and the pathological traits of anxiousness, depressively, emotional lability, and impulsivity. Results confirm the traditional DSM criterion-based BPD diagnosis can be reliably cross-walked with the full AMPD scheme, and both approaches share substantial construct overlap. This relative equivalence suggests the vast clinical and research literatures associated with BPD may be brought forward with DSM-5-III diagnosis of BPD., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Objective: The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions., Methods: A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling., Results: Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia., Conclusions: Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI., (© 2019 The Obesity Society.)

A statistical mediation model was developed within a twin design to investigate the etiology of alcohol use disorder (AUD). Unlike conventional statistical mediation models, this biometric mediation model can detect unobserved confounding. Using a sample of 1410 pairs of Norwegian twins, we investigated specific hypotheses that DSM-IV personality-disorder (PD) traits mediate effects of childhood stressful life events (SLEs) on AUD, and that adulthood SLEs mediate effects of PDs on AUD. Models including borderline PD traits indicated unobserved confounding in phenotypic path coefficients, whereas models including antisocial and impulsive traits did not. More than half of the observed effects of childhood SLEs on adulthood AUD were mediated by adulthood antisocial and impulsive traits. Effects of PD traits on AUD 5‒10 years later were direct rather than mediated by adulthood SLEs. The results and the general approach contribute to triangulation of developmental origins for complex behavioral disorders.

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach., (© 2018 World Psychiatric Association.)

Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects., Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling., Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89., Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors., Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses., Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m2 higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m2 per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood., Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood., (© The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m 2 )], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population., (© 2017 American Society for Nutrition.)

Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI 40-67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct.

Background: The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs., Methods: The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese., Results: OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance., Conclusions: We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve., Competing Interests: The authors declare that no competing interests exist.

Background: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking., Objectives: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments., Design: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling., Results: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions., Conclusions: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity., (© 2016 American Society for Nutrition.)

Estimates of gene-environment interactions (GxE) in behavior genetic models depend on how a phenotype is scaled. Inappropriately scaled phenotypes result in biased estimates of GxE and can sometimes even suggest GxE in the direction opposite to its true direction. Previously proposed solutions are mathematically complex, computationally demanding and may prove impractical for the substantive researcher. We, therefore, evaluated two simple-to-use alternatives: (1) straightforward non-linear transformation of sum scores and (2) factor scores from an appropriate item response theory (IRT) model. Within Purcell's (2002) GxM framework, both alternatives provided less biased parameter estimates, and improved false and true positive rates than using a raw sum score. These approaches are, therefore, recommended over using raw sum scores in tests of GxE. Circumstances under which IRT factor scores versus transformed sum scores should be preferred are discussed.

Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

The heritability of major normative domains of personality is well-established, with approximately half the proportion of variance attributed to genetic differences. In the current study, we examine the possibility of gene × environment interaction (G×E) for adult personality using the environmental context of intimate romantic relationship functioning. Personality and relationship satisfaction are significantly correlated phenotypically, but to date no research has examined how the genetic and environmental components of variance for personality differ as a function of romantic relationship satisfaction. Given the importance of personality for myriad outcomes from work productivity to psychopathology, it is vital to identify variables present in adulthood that may affect the etiology of personality. In the current study, quantitative models of G×E were used to determine whether the genetic and environmental influences on personality differ as a function of relationship satisfaction. We drew from a sample of now-adult twins followed longitudinally from adolescence through age 29. All participants completed the Multidimensional Personality Questionnaire (MPQ) and an abbreviated version of the Dyadic Adjustment Scale. Biometric moderation was found for eight of the eleven MPQ scales examined: well-being, social potency, negative emotionality, alienation, aggression, constraint, traditionalism, and absorption. The pattern of findings differed, suggesting that the ways in which relationship quality moderates the etiology of personality may depend on the personality trait.

Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34-99 (N = 10,681). Fisher's test for mixture distribution of within-monozygotic twin-pair differences (N = 1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories.

Background: The purpose of this study was to characterize the development of BPD symptoms across adolescence by evaluating the fit of several latent variable growth models to annual assessments of symptoms obtained from girls when they were ages 14 through 19 years. After determining the best fitting model, we examined prospective associations between the temperament dimensions of emotionality, activity, low sociability, and shyness and BPD symptom development., Methods: We utilized longitudinal data from the Pittsburgh Girls Study; one of the few large-scale, prospective studies of girls (N = 2,450) in the United States. Parent- and teacher-reports of girls' temperament were collected at Wave 1, when girls were ages 5-8 years. Child-reports of BPD symptoms were collected annually beginning at age 14 through 19 years., Results: We found that a free curve slope intercept model provided the best model fit, with the course of BPD symptoms characterized by a large component of inter-individual stability and a smaller component representing within-individual changes across adolescence. Symptoms appeared to peak by age 15, decline through age 18, and remain steady between ages 18 and 19 years. Both parent- and teacher-reports of temperament emotionality, activity, low sociability, and shyness predicted the developmental course of symptoms., Conclusions: BPD symptoms in adolescence reflect trait-like differences between youth with less within-person variability across time. Childhood temperament dimensions of emotionality, activity, low sociability, and shyness predict adolescent BPD symptom development. Parent- and teacher-informants provide unique information about the course of BPD symptoms, underscoring the utility of collecting child assessments using multiple informants.

This study aims to identify problems in the structure and wording of questions designed to operationalize four DSM-IV diagnostic criteria for alcohol use disorders (AUDs): (1) use of alcohol in hazardous situations (hazard); (2) tolerance; (3) use of alcohol in larger amounts/longer periods than intended (larger/longer); (4) unsuccessful attempts to cut down or control alcohol use (quit/cut down). Ten experts appraised the questions related to these criteria in the WMH-CIDI according to a standardized checklist. These experts identified three main problems: (1) the double-barrelled nature of some of the questions; (2) definitional issues; and (3) unclear thresholds for criterion endorsement. Cognitive interviews of 100 young adult drinkers aged 18-24 were then conducted. The double-barrelled nature of the DSM-IV criteria led to their subsequent over- or under-endorsement. Key terms in the questions under investigation were defined inconsistently. There was also a large amount of variability in the thresholds at which larger/longer and quit/cut down were endorsed. Many of these problems could be linked back to the DSM-IV text. The findings raise questions as to the validity of AUD diagnoses when established via structured diagnostic interview. Further research should focus on testing alternative structure and wording of key AUD criteria to ensure accurate operationalizations of these criteria in structured diagnostic interviews., (Copyright © 2014 John Wiley & Sons, Ltd.)