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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. [ABSTRACT FROM AUTHOR]

Background: Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed overlap among neurodevelopmental problems, and explore whether this potential factor was primarily genetic or environmental in origin. The second aim was to explore whether there was systematic covariation, either genetic or environmental, over and above that contributed by the potential general factor, unique to each syndrome. Method: Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2002 were targeted for interview regarding problems typical of autism spectrum disorders, ADHD and other neurodevelopmental conditions (response rate: 80 percent). Structural equation modeling was conducted on 6,595 pairs to examine the genetic and environmental structure of 53 neurodevelopmental problems. Results: One general genetic factor accounted for a large proportion of the phenotypic covariation among the 53 symptoms. Three specific genetic subfactors identified "impulsivity," "learning problems," and "tics and autism," respectively. Three unique environment factors identified "autism," "hyperactivity and impulsivity," and "inattention and learning problems," respectively. Conclusion: One general genetic factor was responsible for the wide-spread phenotypic overlap among all neurodevelopmental symptoms, highlighting the importance of addressing broad patient needs rather than specific diagnoses. The unique genetic factors may help guide diagnostic nomenclature, whereas the unique environmental factors may highlight that neurodevelopmental symptoms are responsive to change at the individual level and may provide clues into different mechanisms and treatments. Future research would benefit from assessing the general factor separately from specific factors to better understand observed overlap among neurodevelopmental problems.

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]

Background: Research has demonstrated that individuals who identify as a sexual minority (e.g., gay/lesbian, bisexual) are at increased risk for suicidality‐related outcomes. However, previous research is primarily limited by the lack of adjustment for unmeasured (i.e., genetic and environmental) confounding factors and previous psychopathology. Methods: Using the Child and Adolescent Twin Study in Sweden, we employed a co‐twin control design to examine the extent to which the association between sexual orientation and adolescent suicide attempt and self‐harm (SA/SH) was independent of genetic and environmental factors shared by twins, as well as measured symptoms of childhood psychopathology. Results: Adolescents who identified as a sexual minority (i.e., gay/lesbian, bisexual, or other sexual orientation) were at two‐fold increased odds for SA/SH (OR, 2.01 [95% confidence interval, 1.63–2.49) compared to heterosexual adolescents. When adjusting for all genetic and shared environmental factors that make twins similar and for measured childhood psychopathology, the association remained positive but attenuated to OR, 1.55 (1.11–2.16). Conclusions: Identifying as a sexual minority was associated with approximately 50% increased odds of SA/SH in adolescence after adjusting for unmeasured genetic and environmental factors shared by twins and for childhood psychopathology. The results support that environmental factors specifically associated with identifying as a sexual minority likely increase risk for SA/SH. Our findings highlight the need to monitor suicidality risk among this group. [ABSTRACT FROM AUTHOR]

Background: Although attention-deficit hyperactivity disorder (ADHD) is classified as a neurodevelopmental disorder in the latest diagnostic manuals, it shows phenotypic and genetic associations of similar magnitudes across neurodevelopmental, externalising and internalising disorders.Aims: To investigate if ADHD is aetiologically more closely related to neurodevelopmental than externalising or internalising disorder clusters, after accounting for a general psychopathology factor.Method: Full and maternal half-sibling pairs (N = 774 416), born between 1980 and 1995, were identified from the Swedish Medical Birth and Multi-Generation Registers, and ICD diagnoses were obtained from the Swedish National Patient Register. A higher-order confirmatory factor analytic model was fitted to examine associations between ADHD and a general psychopathology factor, as well as a neurodevelopmental, externalising and internalising subfactor. Quantitative genetic modelling was performed to estimate the extent to which genetic, shared and non-shared environmental effects influenced the associations with ADHD.Results: ADHD was significantly and strongly associated with all three factors (r = 0.67-0.75). However, after controlling for a general psychopathology factor, only the association between ADHD and the neurodevelopmental-specific factor remained moderately strong (r = 0.43, 95% CI = 0.42-0.45) and was almost entirely influenced by genetic effects. In contrast, the association between ADHD and the externalising-specific factor was smaller (r = 0.25, 95% CI = 0.24-0.27), and largely influenced by non-shared environmental effects. There remained no internalising-specific factor after accounting for a general factor.Conclusions: Findings suggest that ADHD comorbidity is largely explained by genetically influenced general psychopathology, but the strong link between ADHD and other neurodevelopmental disorders is also substantially driven by unique genetic influences. [ABSTRACT FROM AUTHOR]

The beneficial effects of protons are primarily based on reduction of low to intermediate radiation dose bath to normal tissue surrounding the radiotherapy target volume. Despite promise for reduced long-term toxicity, the percentage of cancer patients treated with proton therapy remains low. This is probably caused by technical improvements in planning and delivery of photon therapy, and by high cost, low availability and lack of high-level evidence on proton therapy. A number of proton treatment facilities are under construction or have recently opened; there are now two operational Scandinavian proton centres and two more are under construction, thereby eliminating the availability hurdle. Even with the advantageous physical properties of protons, there is still substantial ambiguity and no established criteria related to which patients should receive proton therapy. This topic was discussed in a session at the Nordic Collaborative Workshop on Particle Therapy, held in Uppsala 14–15 November 2019. This paper resumes the Nordic-Baltic perspective on proton therapy indications and discusses strategies to identify patients for proton therapy. As for indications, neoplastic entities, target volume localisation, size, internal motion, age, second cancer predisposition, dose escalation and treatment plan comparison based on the as low as reasonably achievable (ALARA) principle or normal tissue complication probability (NTCP) models were discussed. Importantly, the patient selection process should be integrated into the radiotherapy community and emphasis on collaboration across medical specialties, involvement of key decision makers and knowledge dissemination in general are important factors. An active Nordic-Baltic proton therapy organisation would also serve this purpose. [ABSTRACT FROM AUTHOR]

Few quantitative behavior genetic studies have examined why psychopathology is associated with suicide attempt (SA) and self-harm (SH) in adolescence. The present study analyzed data from the Child and Adolescent Twin Study in Sweden to examine the extent to which genetic and environmental factors explain SA/SH and its association with psychopathology in childhood, an often-cited risk factor of subsequent SA/SH. When children were 9 or 12 years old (n = 30,444), parents completed the Autism-Tics, AD/HD and other Comorbidities Inventory (Larson et al., 2010) regarding their children's psychiatric problems as part of an ongoing, longitudinal study. At age 18 years (n = 10,269), adolescents completed self-report questionnaires, including SA/SH assessments. In a bifactor model of childhood psychopathology, a general factor of psychopathology was a statistically significant predictor of adolescent SA/SH at a higher magnitude (β, 0.25, 95% confidence interval [CI; 0.15, 0.34] for suicide attempt), as compared with specific factors of inattention, impulsivity, oppositional behavior, and anxiety/emotion symptoms. Quantitative genetic modeling indicated that the additive genetic influences on the general factor accounted for the association with each outcome (β, 0.24, 95% CI [0.13, 0.34] for suicide attempt). The results remained virtually identical when we fit a higher order factors model. Two additional outcomes demonstrated comparable results. The results extend current literature by revealing the shared genetic overlap between general psychopathology during childhood and adolescent SA/SH. (PsycInfo Database Record (c) 2020 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Importance: It is unclear if the associations between fetal growth and later mental health conditions remain after controlling for familial factors and psychiatric comorbidity.Objective: To examine the associations between fetal growth and general and specific mental health conditions, controlling for familial factors.Design, Setting, and Participants: This register-based study conducted in Sweden analyzed 546 894 pairs of full siblings born between January 1, 1973, and December 31, 1998. Sibling pairs were followed up through December 31, 2013. First, population-based and within-sibling pair associations (which controlled for time-invariant familial confounders) between fetal growth and the outcomes were estimated. Second, exploratory factor analysis was applied to the outcomes to derive 1 general factor and 4 specific and independent factors. Third, the general and specific factors were regressed on fetal growth. Statistical analysis was performed from March 27, 2017, to October 27, 2018.Main Outcome and Measures: The outcomes were 11 psychiatric diagnoses (depression, anxiety, obsessive-compulsive disorder, posttraumatic stress disorder, bipolar disorder, alcohol abuse, drug use, attention-deficit/hyperactivity disorder, autism, schizophrenia, and schizoaffective disorder) and court convictions of violent crimes. Birth weight (in kilograms) statistically adjusted for gestational age was the exposure.Results: The mean (SD) age of the 1 093 788 participants was 27.2 (6.8) years (range, 15.1-40.9 years) and 51.5% were male. Nine outcomes were significantly associated with birth weight in the population at large: depression (odds ratio [OR], 0.96; 95% CI, 0.95-0.98), anxiety (OR, 0.94; 95% CI, 0.92-0.95), posttraumatic stress disorder (OR, 0.91; 95% CI, 0.89-0.93), bipolar disorder (OR, 0.94; 95% CI, 0.89-1.00), alcohol abuse (OR, 0.89; 95% CI, 0.87-0.91), drug use (OR, 0.83; 95% CI, 0.80-0.85), violent crimes (OR, 0.85; 95% CI, 0.83-0.86), attention-deficit/hyperactivity disorder (OR, 0.88; 95% CI, 0.86-0.90), and autism (OR, 0.95; 95% CI, 0.92-0.97). Only depression (OR, 0.95; 95% CI 0.92-0.98), obsessive-compulsive disorder (OR, 0.93; 95% CI, 0.87-0.99), attention-deficit/hyperactivity disorder (OR, 0.86; 95% CI, 0.82-0.89), and autism (OR, 0.72; 95% CI, 0.69-0.76) remained significantly associated within sibling pairs. An exploratory factor analysis indicated that 1 general and 4 specific factors (capturing anxiety, externalizing, neurodevelopmental, and psychotic conditions) fit the outcomes well. Across almost all sensitivity analyses, an increase in birth weight by 1 kg significantly reduced the general (β, -0.047; 95% CI, -0.071 to -0.023) and the specific neurodevelopmental factors (β, -0.159; 95% CI, -0.190 to -0.128) within sibling pairs.Conclusions and Relevance: Controlling for familial confounders, reduced fetal growth was associated with a small but significant increase in the general factor of psychopathology and a moderate increase in a specific neurodevelopmental factor. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD), Attention‐deficit/Hyperactivity disorder (ADHD), and other related neurodevelopmental disorders (NDDs) have, in some previous studies, been shown to increase the risk of being sexually victimized. However, no studies have examined whether the association is driven by a general NDD phenotype versus specific diagnoses, nor the etiology of the association. Method: Using a genetically informative, prospective design, we examined the association between ASD and ADHD in childhood and coercive sexual victimization up to age 18. A total of 4,500 children participating in the Child and Adolescent Twin Study in Sweden (CATSS) were rated by their parents on NDDs at age 9 or 12 years, and self‐reported at age 18 on lifetime experiences of coercive sexual touching and/or coercive sex. First, we regressed sexual victimization on the NDDs. Second, we regressed sexual victimization on general and specific NDD symptoms identified via a bifactor model. Third, we decomposed the observed associations into genetic and environmental parts. Results: In females, ASD was associated with an almost threefolded increased risk of coercive sexual victimization, and ADHD with a doubled risk. In males, the risk associated with ASD and ADHD was of the same magnitude but not significant. When controlling for overall NDD symptom load ASD or ADHD, no longer uniquely predicted coercive sexual victimization. The association between the NDD general factor and coercive sexual victimization was due to shared genetics. Conclusions: General NDD symptom load, rather than specific ASD or ADHD symptoms, seems to be a moderate vulnerability factor for coercive sexual victimization. We speculate that an evocative gene–environment correlation might account for this observation, such that sexual perpetrators actively target NDD individuals. [ABSTRACT FROM AUTHOR]

Bully victimization is a common problem among children with neurodevelopmental disorders, including attention deficit/hyperactivity disorder and autism spectrum disorder. Previous research was mostly cross-sectional and seldom accounted for co-morbid psychopathology, which makes it difficult to draw conclusions about causality and specificity of any association. Using a genetically informative prospective design, we investigated the association between various neurodevelopmental problems (NDPs) in childhood and bully victimization in adolescence, and the relative contributions of genetic and environmental factors to this association. We obtained parent-reports of NDPs at age 9/12 years and self-reported bully victimization at age 15 for 3,921 children participating in the The Child and Adolescent Twin Study in Sweden (CATSS). Structural equation modelling was used to control for NDP co-morbidity and bully victimization at baseline. Cholesky decomposition was used to analyse genetic and environmental contributions to observed associations. Because most of the NDPs were associated to later bully victimization, a common effect of all NDPs was summarized into a general NDP factor. Controlling for this general factor, only problems with social interaction and motor control uniquely predicted subsequent bully victimization in girls. General and unique associations were influenced by both genetic and unique environmental factors. NDPs in general and social interaction and motor problems in particular predicted later bully victimization. The longitudinal design and twin analyses indicated that these associations might be causal. Knowledge of these vulnerabilities may be important when designing risk assessment and prevention strategies. [ABSTRACT FROM AUTHOR]

Background Studies have found an association between low birth weight and ADHD, but the nature of this relation is unclear. First, it is uncertain whether birth weight is associated with both of the ADHD dimensions, inattentiveness and hyperactivity-impulsivity. Second, it remains uncertain whether the association between birth weight and ADHD symptom severity is confounded by familial factors. Method Parents of all Swedish 9- and 12-year-old twins born between 1992 and 2000 were interviewed for DSM- IV inattentive and hyperactive-impulsive ADHD symptoms by the Autism - Tics, AD/ HD and other Comorbidities (A- TAC) inventory ( N = 21,775 twins). Birth weight was collected prospectively through the Medical Birth Registry. We used a within-twin pair design to control for genetic and shared environmental factors. Results Reduced birth weight was significantly associated with a mean increase in total ADHD (β = −.42; 95% CI: −.53, −.30), inattentive (β = −.26; 95% CI: −.33, −.19), and hyperactive-impulsive (β = −.16; 95% CI: −.22, −.10) symptom severity. These results imply that a change of one kilogram of birth weight corresponded to parents rating their child nearly one unit higher (going from 'no' to 'yes, to some extent' on a given symptom) on the total ADHD scale. These associations remained within pairs of MZ and DZ twins, and were also present when restricting the analyses to full term births. Conclusions There is an independent association between low birth weight and all forms of ADHD symptoms, even after controlling for all environmental and genetic confounds shared within twin pairs. These results indicate that fetal growth restriction (as reflected in birth weight differences within twin pairs) and/or the environmental factors which influence it is in the casual pathway leading to ADHD. [ABSTRACT FROM AUTHOR]

Background Autistic-like traits (ALTs) are continuously distributed in the general population, with the autism spectrum disorder (ASD) at the upper extreme end. A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses. Findings We could not replicate the previous association between rs4307059 and social communication impairment. Moreover, common variations in CNTNAP2 (rs7794745 and rs2710102), RELN (rs362691), and SHANK3 (rs9616915) were not significantly associated with ALTs in our study. Conclusions Our results do not suggest that the investigated genes, which previously has been found associated with ASD diagnosis, have any major influence on ALTs in children from the general population. [ABSTRACT FROM AUTHOR]

Background Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed overlap among neurodevelopmental problems, and explore whether this potential factor was primarily genetic or environmental in origin. The second aim was to explore whether there was systematic covariation, either genetic or environmental, over and above that contributed by the potential general factor, unique to each syndrome. Method Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2002 were targeted for interview regarding problems typical of autism spectrum disorders, ADHD and other neurodevelopmental conditions (response rate: 80 percent). Structural equation modeling was conducted on 6,595 pairs to examine the genetic and environmental structure of 53 neurodevelopmental problems. Results One general genetic factor accounted for a large proportion of the phenotypic covariation among the 53 symptoms. Three specific genetic subfactors identified 'impulsivity,' 'learning problems,' and 'tics and autism,' respectively. Three unique environment factors identified 'autism,' 'hyperactivity and impulsivity,' and 'inattention and learning problems,' respectively. Conclusion One general genetic factor was responsible for the wide-spread phenotypic overlap among all neurodevelopmental symptoms, highlighting the importance of addressing broad patient needs rather than specific diagnoses. The unique genetic factors may help guide diagnostic nomenclature, whereas the unique environmental factors may highlight that neurodevelopmental symptoms are responsive to change at the individual level and may provide clues into different mechanisms and treatments. Future research would benefit from assessing the general factor separately from specific factors to better understand observed overlap among neurodevelopmental problems. [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]

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.)

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: 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.)

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.

Background: We examined whether childhood conduct problems predicted a wide range of adverse outcomes in emerging adulthood and whether the association with internalizing problems remained after adjusting for general comorbidity and externalizing problems., Methods: Participants were 18,649 twins from the Child and Adolescent Twin Study in Sweden. At age 9/12, parents rated their children on eight conduct problems. Adverse outcomes were retrieved from national registers in emerging adulthood (median follow-up time = 9.2 years), including diagnoses of six psychiatric disorders, prescriptions of antidepressants, suicide attempts, criminality, high school ineligibility, and social welfare recipiency. We estimated risk for the separate outcomes and examined if conduct problems predicted an internalizing factor above and beyond a general comorbidity and an externalizing factor. We used twin analyses to estimate genetic and environmental contributions to these associations., Results: On the average, each additional conduct symptom in childhood was associated with a 32% increased risk of the adverse outcomes in emerging adulthood (mean hazard ratio = 1.32; range = 1.16, 1.56). A latent childhood conduct problems factor predicted the internalizing factor in emerging adulthood (β boys  = .24, standard error, SE = 0.03; β girls  = .17, SE = 0.03), above and beyond its association with the externalizing (β boys  = 0.21, SE = 0.04; β girls  = 0.17, SE = 0.05) and general factors (β boys  = 0.45, SE = 0.03; β girls  = 0.34, SE = 0.04). These associations were differentially influenced by genetic and environmental factors., Conclusions: It is important to monitor boys and girls with conduct problems not only for future externalizing problems, but also for future internalizing problems. Prevention of specific outcomes, however, might require interventions at different levels., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults., Methods: We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components., Results: At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43)., Conclusions: We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.

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.)