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Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Offspring of parents with bipolar disorder have increased risks of their own psychopathology. However, a large‐scale survey of psychiatric, somatic, and adverse social outcomes up to adulthood, which could aid in prioritizing and tailoring prevention, is lacking. It also remains to clarify how risks are modified by other parental factors.Swedish population registers were linked to compare offspring having (N = 24,788) and not having (N = 247,880) a parent with bipolar disorder with respect to psychiatric diagnoses and psychotropic medication, birth‐related and somatic conditions, social outcomes, accidents, suicide attempts, and mortality. Individuals were followed until age 18. We estimated the influence of lifetime parental psychiatric comorbidity, bipolar disorder subtype, and sex on outcomes.Children of parents with bipolar disorder had 2–3 times higher risks of all psychiatric diagnoses, except for bipolar disorder, for which the risk was 11‐fold. Significantly increased risks were also found for several somatic conditions, low school grades, criminal behavior, victimization, accidents, and suicidal behavior. Adjusting for lifetime parental psychiatric comorbidity attenuated most associations. Offspring of a parent with bipolar disorder type 2 had statistically significantly higher risks of attention deficit hyperactivity disorder, respiratory tract conditions, and accidents compared with offspring of a parent with bipolar disorder type 1. Offspring of mothers with bipolar disorder had higher risks of several psychiatric diagnoses, respiratory tract conditions, low school grades, and accidents compared with offspring of fathers with bipolar disorder. Having two parents with bipolar disorder entailed the highest risks of psychiatric outcomes in offspring.Early intervention and family support are particularly warranted for the offspring of a parent with bipolar disorder in the presence of lifetime parental psychiatric comorbidity, when the parent has bipolar disorder type 2, or when the mother or both parents have bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Although polygenic risk scores (PRS) predict psychiatric problems, these associations might be attributable to indirect pathways including population stratification, assortative mating, or dynastic effects (mediation via parental environments). The goal of this study was to examine whether PRS‐psychiatric symptom associations were attributable to indirect versus direct pathways. Methods: The sample consisted of 3,907 dizygotic (DZ) twin pairs. In childhood, their parents rated them on 98 symptoms. In adolescence (n = 2,393 DZ pairs), both the parents and the twins rated themselves on 20 symptoms. We extracted one general and seven specific factors from the childhood data, and one general and three specific factors from the adolescent data. We then regressed each general factor model onto ten psychiatric PRS simultaneously. We first conducted the regressions between individuals (β) and then within DZ twin pairs (βw), which controls for indirect pathways. Results: In childhood, the PRS for ADHD predicted general psychopathology (β = 0.09, 95% CI: [0.06, 0.12]; βw = 0.07 [0.01, 0.12]). Furthermore, the PRS for ADHD predicted specific inattention (β = 0.04 [0.00, 0.08]; βw = 0.09 [0.01, 0.17]) and specific hyperactivity (β = 0.07 [0.04, 0.11]; βw = 0.09 [0.01, 0.16]); the PRS for schizophrenia predicted specific learning (β = 0.08 [0.03, 0.13]; βw = 0.19 [0.08, 0.30]) and specific inattention problems (β = 0.05 [0.01, 0.09]; βw = 0.10 [0.02, 0.19]); and the PRS for neuroticism predicted specific anxiety (β = 0.06 [0.02, 0.10]; βw = 0.06 [0.00, 0.12]). Overall, the PRS‐general factor associations were similar between individuals and within twin pairs, whereas the PRS‐specific factors associations amplified by 84% within pairs. Conclusions: This implies that PRS‐psychiatric symptom associations did not appear attributable to indirect pathways such as population stratification, assortative mating, or mediation via parental environments. Rather, genetics appeared to directly influence symptomatology. [ABSTRACT FROM AUTHOR]

Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden (n = 18,234 born 1994–2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence. [ABSTRACT FROM AUTHOR]

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits. [ABSTRACT FROM AUTHOR]

Abstract: Electrophoretic NMR (eNMR) and pulsed-field-gradient NMR (PFG-NMR) methods were used to study transport processes in situ and in a chemically resolved manner in the electrolyte of an experimental direct methanol fuel cell (DMFC) setup, constituted of several layers of Nafion 117. The measurements were conducted at room temperature for membranes fully swollen by methanol–water mixtures over a wide concentration interval. The experimental setup and the experimental protocol for the eNMR experiments are discussed in detail. The magnitude of the water and methanol self-diffusion coefficients show a good agreement with previously published data while the ratio of the two self-diffusion coefficients may indicate an imperfect mixing of the two solvent molecules. On the molecular level, the drag of water and methanol molecules by protons is roughly of the same magnitude, with the drag of methanol molecules increasing with increasing methanol content. The electro-osmotic drag defined on mass-flow basis increased for methanol from a low level with increasing methanol concentration while that of water remained roughly constant. [Copyright &y& Elsevier]

Background: Top‐down volitional command of eye movements may serve as a candidate endophenotype of ADHD, an important function underlying goal‐directed action in everyday life. In this twin study, we examined the relation between performance on a response inhibition eye‐tracking paradigm and parent‐rated ADHD traits in a population‐based twin sample. We hypothesized that altered eye movement control is associated with the severity of ADHD traits and that this association is attributable to genetic factors. Methods: A total of 640 twins (320 pairs, 50% monozygotic) aged 9–14 years) from the Child and Adolescent Twin Study in Sweden (CATSS) participated. Twins performed the antisaccade task indexing inhibitory alterations as either direction errors (following exogenous cues rather than instructions) or premature anticipatory eye movements (failure to wait for cues). We calculated the associations of eye movement control and ADHD traits using linear regression mixed‐effects models and genetic and environmental influences with multivariate twin models. Results: Premature anticipatory eye movements were positively associated with inattentive traits (β =.17; 95% CI: 0.04, 0.31), while controlling for hyperactive behaviors and other covariates. Both premature anticipatory eye movements and inattention were heritable (h2 = 0.40, 95% CI: 0.22, 0.56; h2 = 0.55; 95% CI: 0.42, 0.65; respectively), and their genetic correlation was small but statistically significant (r =.19, 95% CI: 0.02, 0.36). However, the genetic correlation did not remain significant after adjusting for covariates (age, sex, hyperactivity traits, IQ). No link was found between direction errors and ADHD traits. Conclusions: This study indicates that there is a specific, genetically influenced, relation between top‐down eye movement control and the inattentive traits typical of ADHD. [ABSTRACT FROM AUTHOR]

Liming with 'structure lime', comprising approximately 80–85% ground limestone and 15–20% slaked lime, has been promoted in subsidised environmental schemes in Sweden since 2010 to increase clay aggregate stability and mitigate particulate phosphorus losses to surface waters. To date, approximately 65,000 ha have been structure-limed. Apart from stabilising aggregates, liming may also improve other physical properties, such as soil strength. This study examined the effect of increasing application rate (0–16 t ha-1) of structure lime on soil strength, approximated by horizontal (draught requirement) and vertical (penetrometer resistance) measurements, in eight field soils (clay content 26–38%) to which structure lime had been applied two, three, four or six years previously. Draught requirement when cultivating with a multipurpose cultivator significantly decreased (by 11%) with the highest application rate of structure lime (16 t ha-1) compared with an unlimed control. This reduced the wheel power requirement by 7.1 kW and diesel consumption by 1.2–1.4 L ha-1, and lowered CO 2 emissions by 3–4 kg ha-1. To clarify the general effect of structure liming, the mean value of all limed treatments was compared with that of the unlimed control. This showed that structure liming in general significantly reduced the draught requirement (by 7%). However, penetrometer resistance measurements revealed no significant effects of structure liming and no relation between draught requirement and penetrometer resistance measurements. Overall, the results indicate that structure liming can reduce fuel consumption, due to easier soil tillage, and thus lower CO 2 emissions. • Cultivator draught requirement was measured in structure limed field trials. • A towing eye with sensors that can measure forces in three directions was used. • Structure liming reduced horizontal draught requirement by 7%. • Reductions corresponded to decreases of 1.2–1.4 L diesel ha-1 and 3–4 kg CO 2 ha-1. • Structure liming did not affect penetrometer resistance in this study. [ABSTRACT FROM AUTHOR]

Background and Purpose: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing., Materials and Methods: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared., Results: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2)., Conclusion: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Associations were examined between six psychiatric diagnoses in parents and a broad range of psychiatric and nonpsychiatric outcomes in their offspring., Methods: All individuals born in Sweden between 1970 and 2000 were linked to their biological parents (N=3,286,293) through Swedish national registers. A matched cohort design, with stratified Cox regression and conditional logistic regression analyses, was used examine associations between six psychiatric diagnoses in the parents and 32 outcomes in their offspring. All children, including those exposed and those not exposed to parents with psychiatric diagnoses, were followed from their date of birth to the date of emigration from Sweden, death, or December 31, 2013, when the offspring were 14-44 years old., Results: In terms of absolute risk, most children who had parents with psychiatric diagnoses were not diagnosed in specialist care themselves, and the proportion of offspring having any of the 16 types of psychiatric conditions ranged from 22.17% (of offspring exposed to parental depression) to 25.05% (of offspring exposed to parental drug-related disorder) at the end of follow-up. Nevertheless, in terms of relative risk, exposure to any of the six parental psychiatric diagnoses increased probabilities of the 32 outcomes among the offspring, with hazard ratios that ranged from 1.03 to 8.46 for time-to-event outcomes and odds ratios that ranged from 1.29 to 3.36 for binary outcomes. Some specificities were observed for parental diagnoses of psychosis and substance-related disorders, which more strongly predicted psychotic-like and externalizing-related outcomes, respectively, in the offspring., Conclusions: The intergenerational transmission of parental psychiatric conditions appeared largely transdiagnostic and extended to nonpsychiatric outcomes in offspring. Given the broad spectrum of associations with the outcomes, service providers (e.g., psychiatrists, teachers, and social workers) should consider clients' broader psychiatric family history when predicting prognosis and planning interventions or treatment., Competing Interests: Dr. Larsson has received grants from Shire Pharmaceuticals; he has received personal fees from and served as a speaker for Evolan Pharma AB, Medice, and Shire/Takeda Pharmaceuticals; he has received sponsorship for a conference on attention deficit hyperactivity disorder from Evolan Pharma AB and Shire/Takeda Pharmaceuticals; and he is the editor-in-chief of JCPP Advances. The other authors report no financial relationships with commercial interests.

Chronic overlapping pain conditions (COPCs) by definition, frequently co-occur, perhaps reflecting their shared etiologies. Their overlapping nature presents a methodological challenge, possibly masking associations between COPCs and health outcomes attributable to either general or specific processes. To address this challenge, we used population-based cohort data to evaluate the predictive validity of a bifactor model of 9 self-reported COPCs by assessing its association with incident pain-related clinical diagnoses; pain-relevant pharmacotherapy; and other health outcomes. We obtained data from a 2005 to 2006 study of Swedish adult twins linked with health data from nationwide registers through 2016 (N = 25,418). We then fit a bifactor model comprising a general COPC factor and 2 independent specific factors measuring pain-related somatic symptoms and neck and shoulder pain. Accounting for age, biological sex, and cancer, the general factor was associated with increased risk of all pain-related outcomes (eg, COPC diagnosis adjusted odds ratio [aOR], 1.71; 95% confidence interval [1.62, 1.81]), most mental health-related outcomes (eg, depression aOR, 1.72 [1.60, 1.85]), and overdose and mortality (eg, all-cause mortality aOR, 1.25 [1.09, 1.43]). The somatic symptoms specific factor was associated with pain-relevant pharmacotherapy (eg, prescribed opioids aOR, 1.25 [1.15, 1.36]), most mental health-related outcomes (eg, depression aOR, 1.95 [1.70, 2.23]), and overdose (eg, nonfatal overdose aOR, 1.66 [1.31, 2.10]). The neck and shoulder pain-specific factor was weakly and inconsistently associated with the outcomes. Findings provide initial support for the validity and utility of a general-factor model of COPCs as a tool to strengthen understanding of co-occurrence, etiology, and consequences of chronic pain. PERSPECTIVE: This article presents associations between a novel measurement model of COPCs and various health outcomes. Findings provide support for measuring pain across multiple domains rather than only measuring pain specific to one physical location in both research and clinical contexts., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability to psychopathology or confounded by unmeasured familial factors. The authors investigated the association between psychiatric conditions in young adulthood and the risk of cardiometabolic complications in middle adulthood, up to 40 years later., Methods: This cohort study (N=672,823) identified all individuals and their siblings born in Sweden between 1955 and 1962 and followed the cohort through 2013. Logistic regression models were used to estimate the bivariate associations between 10 psychiatric conditions or criminal convictions and five cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the comorbidity among psychiatric conditions and criminal convictions. The cardiometabolic complications were then regressed on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs., Results: Each psychiatric condition significantly increased the risk of cardiometabolic complications. These associations appeared nonspecific, as multivariate models indicated that most were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals' general psychopathology and their siblings' cardiometabolic complications. The same pattern was evident for the specific internalizing and psychotic factors., Conclusions: Associations between mental disorders in early life and later long-term risk of cardiometabolic complications appeared to be attributable to a general liability to psychopathology. Familial coaggregation analyses suggested that the elevated risk could not be attributed to confounders shared within families. One possibility is that lifestyle-based interventions may reduce the risk of later cardiometabolic complications for patients with several mental disorders., Competing Interests: Dr. Larsson has received grants from Shire Pharmaceuticals; he has served as a speaker for Evolan Pharma, Medice, and Shire/Takeda Pharmaceuticals; he has received conference sponsorship from Shire/Takeda Pharmaceuticals and Evolan Pharma; and he is editor-in-chief of JCPP Advances. The other authors report no financial relationships with commercial interests.

The spatial distribution of cell surface proteins governs vital processes of the immune system such as intercellular communication and mobility. However, fluorescence microscopy has limited scalability in the multiplexing and throughput needed to drive spatial proteomics discoveries at subcellular level. We present Molecular Pixelation (MPX), an optics-free, DNA sequence-based method for spatial proteomics of single cells using antibody-oligonucleotide conjugates (AOCs) and DNA-based, nanometer-sized molecular pixels. The relative locations of AOCs are inferred by sequentially associating them into local neighborhoods using the sequence-unique DNA pixels, forming >1,000 spatially connected zones per cell in 3D. For each single cell, DNA-sequencing reads are computationally arranged into spatial proteomics networks for 76 proteins. By studying immune cell dynamics using spatial statistics on graph representations of the data, we identify known and new patterns of spatial organization of proteins on chemokine-stimulated T cells, highlighting the potential of MPX in defining cell states by the spatial arrangement of proteins., (© 2024. The Author(s).)

Psychiatric comorbidity can be accounted for by a latent general psychopathology factor (p factor), which quantifies the variance that is shared to varying degrees by every dimension of psychopathology. It is unclear whether the entire continuum of the p factor shares the same genetic origin. We investigated whether mild, moderate, and extreme elevations on the p factor shared the same genetic etiology by, first, examining the linearity of the association between p factors across siblings (N = 580,891 pairs). Second, we estimated the group heritability in a twin sample (N = 17,170 pairs), which involves testing whether the same genetic variants influence both extreme and normal variations in the p factor. In both samples, the p factor was based on 10 register-based psychiatric diagnoses. Results showed that the association between siblings' p factors appeared linear, even into the extreme range. Likewise, the twin group heritabilities ranged from 0.42 to 0.45 (95% CI: 0.33-0.57) depending on the thresholds defining the probands (2-3.33 SD beyond the mean; >2 SD beyond the mean; >4.33 SD beyond the mean; and >5.33 SD beyond the mean), and these estimates were highly similar to the estimated individual differences heritability (0.41, 95% CI: 0.39-0.43), indicating that scores above and below these thresholds shared a common genetic origin. Together, these results suggest that the entire continuum of the p factor shares the same genetic origin, with common genetic variants likely playing an important role. This implies, first, genetic risk factors for the aspect that is shared between all forms of psychopathology (i.e., genetic risk factors for the p factor) might be generalizable between population-based cohorts with a higher prevalence of milder cases, and clinical samples with a preponderance of more severe cases. Second, prioritizing low-cost genome-wide association studies capable of identifying common genetic variants, rather than expensive whole genome sequencing that can identify rare variants, may increase the efficiency when studying the genetic architecture of the p factor., (© 2024. The Author(s).)

Background: Proton radiotherapy treatment plans are currently restricted by the range uncertainties originating from the stopping power ratio (SPR) prediction based on single-energy computed tomography (SECT). Various studies have shown that multi-energy CT (MECT) can reduce the range uncertainties due to medical implant materials and age-related variations in tissue composition. None of these has directly applied the basis material density (MD) images produced by projection-based MECT systems for SPR prediction., Purpose: To present and evaluate a novel proton SPR prediction method based on MD images from dual-energy CT (DECT), which could reduce the range uncertainties currently associated with proton radiotherapy., Methods: A theoretical basis material decomposition into water and iodine material densities was performed for various pediatric and adult human reference tissues, as well as other non-tissue materials, by minimizing the root-mean-square relative attenuation error in the energy interval from 40 to 140 keV. A model (here called MD-SPR) mapping predicted MDs to theoretically calculated reference SPRs was created with locally weighted scatterplot smoothing (LOWESS) data-fitting. The goodness of fit of the MD-SPR model was evaluated for the included reference tissues. MD images of two electron density phantoms, combined to form a head- and an abdomen-sized phantom setup, were acquired with a clinical projection-based fast-kV switching DECT scanner. The MD images were compared to the theoretically predicted MDs of the tissue surrogates and other non-tissue materials in the phantoms, as well as used for input to the MD-SPR model for generation of SPR images. The SPR images were subsequently compared to theoretical reference SPRs of the materials in the phantoms, as well as to SPR images from a commercial algorithm (DirectSPR, Siemens Healthineers, Forchheim, Germany) using image-based consecutive scan DECT for the same phantom setups., Results: The predicted SPRs of the tissue surrogates were similar for MD-SPR and DirectSPR, where the adipose and bone tissue surrogates were within 1% difference to the reference SPRs, while other non-adipose soft tissue surrogates (breast, brain, liver, muscle) were all underestimated by between -0.7% and -1.8%. The SPRs of the non-tissue materials (polymethyl methacrylate (PMMA), polyether ether ketone (PEEK), graphite and Teflon) were within 2.8% for MD-SPR images, compared to 6.8% for DirectSPR., Conclusions: The MD-SPR model performed similar compared to other published methods for the human reference tissues. The SPR prediction for tissue surrogates was similar to DirectSPR and showed potential to improve SPR prediction for non-tissue materials., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Importance: Psychiatric conditions in parents are associated with many psychiatric and nonpsychiatric outcomes in offspring. However, it remains unknown whether this intergenerational transmission is attributable to broader psychopathology comorbidity or to specific conditions., Objective: To estimate associations between general and specific psychopathology factors in parents and a wide range of register-based outcomes in their offspring., Design, Setting, and Participants: This Swedish national register-based cohort study included 2 947 703 individuals born between 1970 and 2000 and followed up with participants through December 31, 2013. Statistical analysis was performed from October 2022 to October 2023., Exposures: Hierarchical factor model consisting of 1 general and 3 specific psychopathology factors fit to 9 parental psychiatric diagnoses and violent criminal court convictions., Main Outcomes and Measures: A total of 31 outcomes were measured in offspring and sorted into 6 broad clusters: psychotic-like outcomes, neurodevelopmental outcomes, internalizing outcomes, externalizing outcomes, behavior and accidents, and psychosocial outcomes., Results: Of 2 947 703 individuals, 1 518 252 (51.5%) were male, and the mean (SD) age at the end of follow-up was 28.7 (8.9) years. The general psychopathology factor in parents was significantly associated with all 31 offspring outcomes (range: odds ratio [OR] for accidents, 1.08 [95% CI, 1.07-1.08] to OR for social welfare recipiency, 1.40 [95% CI, 1.39-1.40]), which means that children whose parents scored 1 SD above the mean on the general psychopathology factor had an 8% to 40% higher odds of different studied outcomes. The specific psychotic factor in parents was primarily associated with all 5 psychotic-like outcomes (range: OR for prescription of antiepileptics, 1.05 [95% CI, 1.04-1.06] to OR for schizophrenia, 1.25 [95% CI, 1.23-1.28]) and the specific internalizing factor in parents was primarily associated with all 6 internalizing outcomes (range: OR for prescription of anxiolytics, 1.10 [95% CI, 1.09-1.10] to OR for depression, 1.13 [95% CI, 1.12-1.13]) and all 6 neurodevelopmental outcomes (range: OR for intellectual disability, 1.02 [95% CI, 1.01-1.03] to OR for autism spectrum disorder, 1.10 [95% CI, 1.09-1.11]) in offspring. The specific externalizing factor in parents was associated with all 6 externalizing outcomes (range: OR for violent crimes, 1.21 [95% CI, 1.19-1.23] to OR for oppositional defiant disorder, 1.32 [95% CI, 1.32-1.33]) and all 6 internalizing outcomes (range: OR for obsessive-compulsive disorder, 1.01 [95% CI, 1.00-1.02] to OR for posttraumatic stress disorder, 1.13 [95% CI, 1.12-1.13]) in offspring., Conclusions and Relevance: This cohort study of the Swedish population suggests that the intergenerational transmission of psychiatric conditions across different types of spectra may largely be attributable to a parental general psychopathology factor, whereas specific factors appeared to be primarily responsible for within-spectrum associations between parents and their offspring. Professionals who work with children (eg, child psychologists, psychiatrists, teachers, and social workers) might benefit from taking the total number of parental psychiatric conditions into account, regardless of type, when forecasting child mental health and social functions.

All psychiatric phenomena are positively associated, and several different models can account for this observation. These include the correlated factors, network, general psychopathology as outcome, and hierarchical models. Advantages of hierarchical models, which consist of one general and several (general factor-residualized) specific factors, is that the general factor provides an opportunity to reliably measure global distress and impairment, while the specific factors might improve the ability to discriminate between individuals with different kinds of problems. Nevertheless, other models also have their respective advantages, and it remains challenging to empirically determine which model best accounts for the positive manifold in psychiatry. Instead, I present two non-empirical arguments in favor of hierarchical models. First, by measuring the general factor in isolation, the specific factors tend to include both favorable and unfavorable correlates, which might reduce stigma compared to psychiatric diagnoses that by and large are associated with only unfavorable outcomes. Second, the general psychopathology factor displays an unusual psychometric property in that it includes symptoms of opposite meaning if they have similar valence (e.g., self-reported symptoms such as gullible and paranoid , lazy and workaholic , and terrified and apathetic load in the same direction), which one might want to measure in isolation from variance capturing the content of symptoms. I conclude by speculating that tests designed based on hierarchical models might help clinical assessment., Competing Interests: The author has declared that he has no competing or potential conflicts of interest., (© 2023 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Importance: General and specific factors of psychopathology are associated with future adverse outcomes, indicating that they might be useful for identifying individuals at greatest risk. However, it remains unknown if these associations are attributable to confounders that may influence both the psychopathology factors and later outcomes., Objective: To analyze associations between psychopathology factors and clinically relevant outcomes within family pairs, adjusting for unmeasured confounds by applying co-twin control and sibling comparison designs., Design, Setting, and Participants: This longitudinal cohort study with a follow-up range of 9 to 13 years included all Swedish twins born from 1959 to 1985 who participated in the Study of Twin Adults: Genes and Environment (60% response rate) and the oldest pair of all Swedish siblings born from 1959 to 1985 per the Multi-Generation Register. Twins were evaluated based on responses to a hierarchical factor model derived using multivariate statistics. Sibling pairs were evaluated based on psychiatric diagnoses per the Swedish National Patient Register. Information on outcome events and prescriptions were derived from the National Patient Register, Prescribed Drug Register, and Crime Register. Baseline assessment was in August 2005, and data were analyzed from January 2022 to February 2023., Exposures: Hierarchical factor model consisting of 1 general and 4 specific factors fit to 48 psychiatric symptoms on which twin participants self-reported in 2005 and 1 general and 3 specific factors fit to 9 register-based psychiatric diagnoses assigned to sibling participants prior to 2005., Main Outcomes and Measures: Outcomes consisted of 7 register-based events occurring after 2005, including suicidal behavior, substance overdoses, and criminal suspicion or convictions (data available until the end of 2013), and prescription of antidepressants, antialcohol or antiopioid medication, antipsychotics, and stimulants (data available until the end of 2017)., Results: The study included 32 328 twins (mean [SD] age, 34 [8] years; 16 076 [49.73%] male) and 1 942 106 siblings (mean [SD] age, 34 [7] years; 991 500 [51.05%] male). General psychopathology was significantly associated with all 7 outcomes within sibling pairs (mean within-pair odds ratio [OR], 2.28; 95% CI, 2.19-2.37) and dizygotic twin pairs (within-pairs OR, 1.65; 95% CI, 1.38-1.98) and with 3 outcomes within monozygotic twin pairs (mean within-pairs OR, 1.77; 95% CI, 1.35-2.36). Within sibling pairs, the specific internalizing factor was associated with antidepressant prescriptions (within-pairs OR, 1.65; 95% CI, 1.59-1.71), the specific substance misuse factor was associated prescription of antialcohol and antiopioid medication (within-pairs OR, 2.36; 95% CI, 2.20-2.54), and the specific psychotic factor was associated with antipsychotic medications (within-pairs OR, 1.61; 95% CI, 1.51-1.72). Similar results emerged within twin pairs., Conclusion and Relevance: In this cohort study, general psychopathology was significantly associated with all 7 outcomes within sibling and dizygotic twin pairs and 3 outcomes within monozygotic twin pairs at 10 years. Within twin and sibling pairs, the specific factors were primarily associated with related outcomes. Several of the associations in this cohort study could not be attributed to unmeasured confounds shared by family members, suggesting that interventions toward broad psychopathology dimensions might help reduce the risk of future clinically relevant events.

Background: Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood., Methods: Individuals born in Sweden 1985-1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems., Results: Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43-2.70) and females (HR 5.39; 95% CI 4.97-5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06-1.51) and females (HR 1.69; 95% CI 1.21-2.36)., Conclusions: Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

Purpose: To examine the association between dispositional optimism and all-cause mortality after esophageal cancer surgery and whether pathological tumor stage and the COVID-19 pandemic modified this association., Methods: This nationwide, population-based prospective cohort study included 335 patients undergoing esophageal cancer surgery in Sweden between January 1, 2013, and December 31, 2019. Dispositional optimism was measured 1 year post-surgery using Life Orientation Test-Revised (LOT-R). A higher LOT-R sum score represents higher dispositional optimism. Mortality information was obtained from the Swedish Register of the Total Population. All patients were followed up until death or until December 31, 2020, whichever occurred first. Cox regression with adjustments for confounders was used., Results: The median follow-up was 20.8 months, during which 125 (37.3%) patients died. Among the included 335 patients, 219 (65.4%) patients had tumor pathologically staged Tis-II, and 300 (89.6%) patients entered the cohort before the COVID-19 pandemic. Both tumor stage and the COVID-19 pandemic were effect modifiers. For each unit increase in LOT-R sum score, the risk of all-cause mortality decreased by 11% (HR 0.89, 95% CI 0.81 to 0.98) among patients with tumor staged Tis-II before the COVID-19 pandemic. This association was non-significant in patients with tumor staged III-IV (HR 0.99, 95% CI 0.92 to 1.07) and during the COVID-19 pandemic (HR 1.08, 95% CI 0.94 to 1.25)., Conclusion: Assessing dispositional optimism may help predict postoperative survival, especially for patients with early and intermediate esophageal cancer. Increasing dispositional optimism might be a potential intervention target to improve survival after esophageal cancer surgery., (© 2022. The Author(s).)

Purpose: To examine the trajectory of psychological distress from 1 to 2 years after esophageal cancer surgery, and whether dispositional optimism could predict the risk of postoperative psychological distress., Methods: This Swedish nationwide longitudinal study included 192 patients who had survived for 1 year after esophageal cancer surgery. We measured dispositional optimism with the Life Orientation Test-Revised (LOT-R) 1 year post-surgery and psychological distress with the Hospital Anxiety and Depression Scale 1, 1.5, and 2 years post-surgery. Latent growth curve models were used to assess the trajectory of postoperative psychological distress and to examine the predictive validity of dispositional optimism., Results: One year after surgery, 11.5% (22 of 192) patients reported clinically significant psychological distress, and the proportion increased to 18.8% at 1.5 years and to 25.0% at 2 years post-surgery. Higher dispositional optimism predicted a lower probability of self-reported psychological distress at 1, 1.5, and 2 years after esophageal cancer surgery. For each point increase in the LOT-R sum score, the odds of psychological distress decreased by 44% (OR, 0.56; 95% CI, 0.40 to 0.79)., Conclusion: The high prevalence and longitudinal increase of self-reported psychological distress after esophageal cancer surgery indicate the unmet demands for timely psychological screening and interventions. Measuring dispositional optimism may help identify patients at higher risk of developing psychological distress, thereby contributing to the prevention of postoperative psychological distress., (© 2021. The Author(s).)

Purpose: To assess whether higher dispositional optimism could predict better health-related quality of life (HRQL) after esophageal cancer surgery., Methods: This Swedish nationwide longitudinal study included 192 patients who underwent esophagectomy for cancer. The exposure was dispositional optimism measured by the Life Orientation Test-Revised (LOT-R) at 1 year post-surgery. Patients were categorized into four subgroups (very low, moderately low, moderately high, and very high dispositional optimism) based on the quartile of the LOT-R sum score. The outcome was HRQL assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Esophago-Gastric module 25 (QLQ-OG25) at 1, 1.5, and 2 years post-surgery. Linear mixed-effects models, adjusted for potential confounders, were used to examine the mean score difference (MSD) with 95% confidence interval of HRQL among the four patient subgroups., Results: Patients with very high dispositional optimism reported clinically relevantly better global quality of life, emotional function, and social function (MSD range 10-16) and less severe symptoms in pain, dyspnea, diarrhea, eating difficulty, anxiety, dry mouth, trouble with taste, worry about weight loss, and self-doubt about body image (MSD range - 9 to - 22) than patients with lower dispositional optimism. Patients with moderately high dispositional optimism reported clinically and statistically significantly better global quality of life (MSD 10) and less severe diarrhea (MSD - 9) than patients with lower dispositional optimism. Adjusted MSDs were constant over the three time points in all aspects except for eating difficulty., Conclusions: Measuring dispositional optimism could help identify patients at higher risk of poor HRQL recovery after esophageal cancer surgery., (© 2021. The Author(s).)

Purpose: The aim of the study was to investigate the magnitude of an independent association between bullying victimization and self-harm and suicide attempt in adolescence after adjusting for unmeasured and measured confounding factors., Methods: Using the Child and Adolescent Twin Study in Sweden, we examined twins born between 1994 and 1999 (n = 13,852). Twins self-reported bullying victimization at age 15 years and self-harm and suicide attempt at age 18 years. We created a factor score of 13 bullying items, on which self-harm and suicide attempt items were regressed in three models: (1) among unrelated individuals; (2) among co-twins, in which a twin exposed to more bullying was compared with his/her co-twin who was exposed to less; and (3) among co-twins while adjusting for indicators of childhood psychopathology., Results: Among unrelated individuals, a one standard deviation increase in bullying victimization was associated with increased odds for self-harm (odds ratio [OR], 1.29 [95% confidence interval, 1.23-1.36]) and suicide attempt (OR, 1.68 [1.53-1.85]). Among co-twins, the odds attenuated for self-harm (OR, 1.19 [1.09-1.30]) and suicide attempt (OR, 1.39 [1.17-1.66]). Finally, when accounting for childhood psychopathology, there was a 14% (1.04-1.25) and 25% (1.03-1.52) relative increase in odds of self-harm and suicide attempt, respectively., Conclusions: The results suggest that bullying victimization was uniquely associated with self-harm and suicide attempt over and above the confounding because of unmeasured and measured factors (i.e., familial vulnerability and pre-existing psychopathy). However, magnitudes were small, suggesting that additional interventions and screenings are needed to address suicidality apart from bullying interventions., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Understanding the dynamics of the human proteome is crucial for developing biomarkers to be used as measurable indicators for disease severity and progression, patient stratification, and drug development. The Proximity Extension Assay (PEA) is a technology that translates protein information into actionable knowledge by linking protein-specific antibodies to DNA-encoded tags. In this report we demonstrate how we have combined the unique PEA technology with an innovative and automated sample preparation and high-throughput sequencing readout enabling parallel measurement of nearly 1500 proteins in 96 samples generating close to 150,000 data points per run. This advancement will have a major impact on the discovery of new biomarkers for disease prediction and prognosis and contribute to the development of the rapidly evolving fields of wellness monitoring and precision medicine., Competing Interests: Conflict of interest All authors are employees of Olink Proteomics AB commercializing the described method. An author may or may not be named as an inventor on current patents owned and controlled by Olink Proteomics AB, https://www.olink.com/patents/, as amended from time to time. All authors have financial interest in Olink Holding AB., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigated the association between the ability to maintain prolonged (2-minute) fixation on a visual target and ADHD traits in a sample consisting of 120 monozygotic and 120 dizygotic twin pairs, aged 9 to 14 years. More intrusive saccades during the task was associated with higher level of parent-reported ADHD traits. Both intrusive saccades and ADHD symptoms had high heritability estimates, and there was a moderate genetic correlation between number of intrusive saccades and ADHD. This study suggests that inability to maintain ocular fixation for longer times is etiologically linked to ADHD traits in the general population., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Common genetic risk variants have been implicated in the etiology of clinical attention-deficit/hyperactivity disorder (ADHD) diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric symptoms, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing, and internalizing symptoms, using structural equation modeling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing, and depressive symptoms (R 2  = 0.26-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading = 0.50, range = 0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~ 1% (p value < 0.0001) of the variance in the general psychopathology factor and ~ 0.50% (p value < 0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.

Visual disengagement has been hypothesized as an endophenotype for autism. In this study we used twin modelling to assess the role of genetics in basic measures of visual disengagement, and tested their putative association to autistic traits in the general population. We used the Gap Overlap task in a sample of 492 twins. Results showed that most of the covariance among eye movement latencies across conditions was shared and primarily genetic. Further, there were unique genetic contributions to the Gap condition, but not to the Overlap condition-i.e. the one theorized to capture visual disengagement. We found no phenotypic association between autistic traits and disengagement, thus not supporting the hypothesis of visual disengagement as an endophenotype for autistic traits.

Background and Purpose: Metal artefacts in computed tomography (CT) images impairs structure delineation. These artefacts can potentially be reduced with dual-energy CT (DECT) with or without using metal artefact reduction (MAR). The purpose was to investigate how structure delineation in DECT with or without MAR and single-energy CT (SECT) images were affected by metals., Materials and Methods: A phantom with known irregular structures was developed. Reference structures were determined from a low-noise scan without metal. Bilateral hip prostheses were simulated with steel or titanium inserts. The phantom was scanned with SECT and fast-kV switching DECT with optional MAR. Four radiation oncologists delineated the structures in two phantom set-ups. Delineated structures were evaluated with Dice similarity coefficient (DSC) and Hausdorff distance relative to the reference structures., Results: With titanium inserts, more structures were detected for non-MAR DECT compared to SECT while the same or less were detected with steel inserts. MAR improved delineation in DECT images. For steel inserts, three structures in the region of artefacts, were delineated by at least two oncologists with MAR-DECT compared to none with non-MAR DECT or SECT. The highest values of DSC for MAR-DECT were 0.69, 0.81 and 0.77 for those structures., Conclusions: Delineation was improved with non-MAR DECT compared to SECT, especially for titanium inserts. A larger improvement was seen with the use of MAR for both steel and titanium inserts. The improvement was dependent on the location of the structure relative to the inserts, and the structure contrast relative to the background., (© 2019 The Authors.)

Objective: We examined whether a parent-rated general factor of psychopathology in childhood would predict independently measured, severe adverse mental health outcomes in adolescence., Method: We used the Child and Adolescent Twin Study in Sweden, which targets all twin children in Sweden. Parents rated their children (N = 16,806) on 43 symptoms of inattention, hyperactivity/impulsivity, conduct problems, and anxiety/emotionality when the twins turned 9 or 12 years of age. Adverse mental health outcomes in adolescence were retrieved from national registers, and included psychiatric diagnoses, prescription of anxiolytic or antidepressant medication, court convictions of crimes, and failure to achieve eligibility for high school., Results: Parent-rated inattention, hyperactivity/impulsivity, conduct problems, and anxiety/emotionality in childhood predicted all adverse mental health outcomes in adolescence (mean odds ratio = 1.76; range = 1.41-2.18; all p < .05). However, several of these associations were nonsignificant in a multiple regression framework, suggesting the influence of common variance. A general factor of psychopathology uniquely predicted all outcomes (mean odds ratio = 1.58; range = 1.34-1.84; all p < .05), whereas the specific factors predicted only a subset of the outcomes., Conclusion: Mental health problems in childhood are associated with a host of adverse outcomes in adolescence, and, to a considerable extent, these associations are driven by a general factor of psychopathology. The general factor may therefore be important to clinical prognosis, which informs clinical decision making for children., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Autism spectrum disorder (ASD) has been associated with gastrointestinal (GI) problems, but the nature of this association is unclear. Parents to siblings, concordant or discordant for ASD (N = 217), participated in a web survey covering mother's weight gain during pregnancy, maternal viral/bacterial infection and use of antibiotics, duration of breastfeeding, mode of delivery, birth weight and child GI problems. ASD was associated with GI problems and perinatal environmental risk, based on a summation of maternal infection and antibiotic use during pregnancy and/or the breastfeeding period. The association between GI problems and ASD remained within the sibling pairs (β = 1.23; p < .001) in the adjusted model. Our results indicate non-shared environmental effects on the ASD/GI association, but none of the factors examined explained the link.

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.

Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)